2000-2001Annual Report
The Royal DanishSchool of Pharmacy
The Royal Danish School of Pharmacy
Annual Report 2000-2001
ISSN 0905-3913
Editor: Jesper Munck (The Royal Danish School of Pharmacy)
Graphic design / AD: Mads Frederik
Print: Centraltrykkeriet Skive
Photos: Mikal Schlosser, Jesper Munck a.o.
The Royal Danish School of Pharmacy
Universitetsparken 2
DK-2100 Copenhagen
Phone: +45 35 30 60 00
Fax: +45 35 30 60 01
E-mail: [email protected]
Internet: www.dfh.dk
ANNUAL REPORT 2000–2001
PAGE 2
Contents
ANNUAL REPORT 2000–2001
PAGE 3
PAGE
STRENGTHENING OUR ACADEMIC PLATFORM FOR TOMORROW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
IN RETROSPECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
THE STUDY BOARD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
PHAMACOTHERAPY – A NEW SUBJECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
MANAGEMENT AND ORGANISATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
FINANCIAL STATEMENT 2001 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
STUDENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
RESEARCH CENTRES AT THE ROYAL DANISH SCHOOL OF PHARMACY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
PHD DEGREE PROGRAMME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
SPECIALISATION IN COMMUNITY PHARMACY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
THE DEPARTMENTS
DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
DEPARTMENT OF MEDICINAL CHEMISTRY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
DEPARTMENT OF PHARMACEUTICS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
DEPARTMENT OF PHARMACOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
DEPARTMENT OF SOCIAL PHARMACY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
THE DANISH PHARMACEUTICAL LIBRARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
PUBLICATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
MASTER’S THESES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
STAFF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
The Royal Danish School of Pharmacy:
Strengthening our academic platform for tomorrow
The Royal Danish School of Pharmacy has signed a perfor-
mance contract with the Ministry of Science, Technology and
Innovation under which we agree to implement various teach-
ing and research initiatives. A contract like this places every-
one at the School of Pharmacy, staff as well as students, un-
der an obligation to contribute continuously to our academic
development. The contract also requires management to de-
velop our human resources policy to keep the School in the
ANNUAL REPORT 2000–2001
Professor, Dsc
(pharm) Povl
Krogsgaard-Larsen
– rector of The
Royal Danish
School of
Pharmacy
PAGE 4
forefront and provide challenges and interesting work for
everyone involved. Everyone is a player in and contributor to
this complex and multifaceted process.
The performance contract provides a framework and objec-
tives for the School. However, at the same time we must
recognise that the School is on its way into a new academic
era. Our working sphere, the field of pharmaceutical sciences
is undergoing rapid change. Major transformations in this
wide academic field, are coupled with the dramatic biomedi-
cal developments of the post-genomic period we now live in.
As the only Danish pharmaceutical institution with research-
based teaching, the School is at the hub of this accelerating
process, which poses major structural and functional chal-
lenges. Although the new situation has enormous potential for
the School, the prerequisite for realising these prospects is
that we show the will and the strength to be effective players
with external partners whose support is absolutely essential
to the process of change.
Many more pharmacists needed
The powerful reinforcement of the fields of biology and bio-
medicine has resulted in a formidable expansion of the basic
knowledge of medical science. The pharmaceutical disci-
plines often set the effeciency in the transformation of medical
knowledge into new drugs and therapies. This factor has al-
ready created bottlenecks, particularly in the pharmaceutical
industry, while the School is under pressure in terms of re-
sources and recruitment. The forecast is that the need for
pharmacists with MSc and PhD degrees in clinical pharmacy
will grow dramatically in the years ahead. In addition we face
mounting pressure from the pharmacy sector to meet their
urgent need for pharmacists. In response we must make
every effort to mobilise resources so that the School’s re-
search capacity as well as MSc and PhD programmes can be
exploited to the full. In the longer term, we must expand the
School’s combined education and research capacity to match
the rapid development of the research-based pharmaceutical
industry and biotechnology sector. The School’s goal must be
to live up to expectations to educate a sufficient number of
key pharmaceutical experts at the MSc and PhD levels in all
relevant branches of the pharmaceutical sphere.
Unrealistic to educate pharmacists at other sites
In order to increase the number of pharmacy graduates, it
has been suggested to establish a pharmaceutical faculty at
the University of Aarhus or University of Southern Denmark in
Odense. The idea has merit on several grounds, as another
institution to provide pharmaceutical education and research
would be desirable, if implementation of a full programme
were possible. However, such an initiative must be consid-
ered unrealistic, at any rate within the next decade or so. We
simply do not have the teaching capacity, and the current dif-
ficulty in recruiting new students to the field presents a seri-
ous obstacle to initiatives of this kind. It is highly improbable
that the universities in either Aarhus or Odense have envi-
sioned establishing a new full-scale pharmaceutical depart-
ment. The idea probably is to add biology masters’ pro-
grammes to their existing chemistry programmes in order to
offer degrees targeted specifically at the pharmaceutical in-
dustry. However, establishing special sector-oriented pharma-
ceutical studies would create problems. The most obvious
solution to the capacity problem would be to expand the
School’s educational capacity by 25-30%. An expansion of
such magnitude would require additional teaching facilities,
new buildings to some extent, and the infusion of the requi-
site financial resources. We have a compelling need to make
THE RECTORS REPORT
The current difficulty in recruiting new students makes the idea of establishing additional pharma-
ceutical faculties unrealistic.
PAGE 5
detailed plans along these guidelines, and to develop a new
educational structure that will stimulate a dynamic interplay
between pharmacy degree programmes and other university
programmes.
The structure and academic profile
of The Royal Danish School of Pharmacy
The future structure and academic profile of the School has
been the subject of extensive debate over the summer and
autumn. Staff and students have been involved in the debate
in a hectic round of meetings. The extent to which the School’s
departmental structure is the best framework for dynamic
educational and research development was questioned. This
issue is central considering the weight that the School attach-
es to disciplinary integration. In addition, however, the discus-
sion on structure also had the important function of fuelling
debate on the School’s academic development in terms of
teaching and research.
This discussion has been promising and constructive, ini-
tially pinpointing some disciplines that warrant special atten-
tion. The decision was made to continue the process of
defining special focus areas that will be dealt with effectively
by working groups with the aim of finding optimal solutions
for integrating disciplines at Master’s level. Initial focus will be
on the area comprising social pharmacy, clinical pharmacy,
pharmacotherapy and pharmacology. These key disciplines
have wide potential, not only in relation to the clinical area but
also very much in connection with the pharmacy sector.
Teaching in physical chemistry is another area of focus.
Physical chemistry is increasingly a vital component in almost
all branches of pharmacy and thus a subject that involves
teachers and students from all departments. Other disciplines
are on the drawing board and will be made into focus areas
in future.
Key role for the Study Board
Naturally, the Study Board holds a key position in discussions
about the academic development of the School. The Study
Board had already started a wide variety of initiatives, such as
revising Degree Regulations and introducing several new
courses. One new initiative I would like to mention in particu-
lar is a compulsory course in the theory of science. Many
hours were devoted to drawing up a new ministerial order for
the master’s degree in pharmacy and for introducing ICT-
based teaching.
The work on the focus areas mentioned above will largely
fall to the Study Board, but will be accomplished by the man-
agement of the School of Pharmacy. In light of the diversity of
the Study Board’s tasks, an ongoing assessment will be
made of the extent to which they could be handled by the
Programme Administration. Insofar as implementation of new
and changed programme modules will imply changes in the
departmental structure of the School, the Senate
(Konsistorium) will naturally be involved in decision-making.
Closing down centres
In terms of research, the year under review was affected by
the political decision to close down the two inter-institutional
centres under the School, Drug Design and Transport and
NeuroScience PharmaBiotec, at the end of their respective
appropriation periods on 31 October and 31 December 2001.
Other centres of corresponding inter-institutional character
were also closed by political fiat. The two centres under the
auspices of the School were closed despite the very positive
international evaluation of their research results as well as the
development and continuation of close cooperation with the
drug industry generated by their activities. This complemen-
tary cooperation between industrial scientists and scientists
at the School, based on mutual trust, is a strong facet of the
School’s research profile.
In contrast, we are pleased that the Drug Design and
Transport Centre has been granted sustenance funds for a
four-year period corresponding to about 25% of the centre’s
appropriation. Only two other centres that were closed down
at other institutions were allocated sustenance funds on a
similar level. Thus we find it positive that the precedent has
been set for continuing and further developing the research
training activities developed in cooperation with the drug in-
dustry within the framework of the two centres under the
School.
Good research development
Research continues to develop well at the School, with the
group of younger scientists increasingly mastering and man-
aging its course. In 2001 many junior as well as senior scien-
tists attracted research funds from external sources. These
research resources have major impact on all academic devel-
opment at the School as well as for the international status of
the individual scientist. It is not possible to list all of those
who have helped put the School on the international research
map. However, special mention must be made of Professor
Mikael Begtrup, who received the prestigious Chemistry
Award from the Carlsberg Foundation, and Anders Asbjørn
Jensen, assistant research professor, who was awarded the
PhD Prize by the Danish Academy of Natural Sciences. Finally
I would like to mention Dung Ngoc Do, precision instrument
maker and a graduate of the School, who received a distin-
guished bronze medal and well-deserved royal handshake for
his apprenticeship project.
In order to combine and reinforce research at the School
and continue to profile research both nationally and interna-
tionally, the decision has been made to set up a number of
strategic focus areas at the School. This new initiative is ex-
pected to lead to a limited number, perhaps four to six, of
ANNUAL REPORT 2000–2001
PAGE 6
such areas at the School. The ini-
tiative will strengthen and promote
the integration of strong relevant
research areas, and it is expected
that these strategic focus areas to-
gether with other national and in-
ternational research groups will be
able to attract external research
funding.
Research training programmes
The School gives high priority to
research training. Over the years
the School has graduated a large
number of PhDs, both research
pharmacists and graduates with a
different background. When re-
search centres were set up at the
School in 1997, the Graduate
School of Drug Research was es-
tablished on the basis of an alloca-
tion from the then Research
Academy. In the three years since
then the Graduate School of Drug
Research has been the framework
for numerous scientific arrange-
ments targeted at the PhD pro-
gramme. The Graduate School has
also established a total of 15 PhD
scholarships co-financed by the
School, the Research Academy
and industry. Cooperation on grad-
uate studies intensified relations
between the School and other in-
stitutions tied to the centres and the drug industry. An impor-
tant part of this close cooperation is the role of industrial re-
searchers as co-supervisors for PhD students. In recognition
of this activity Novo Nordisk A/S, represented by Professor
Børge Diderichsen, Director of Corporate Research Affairs,
granted DKK 450,000 to award the Novo Nordisk PhD Plus
Prize in recognition of particularly talented PhD students or
PhD graduates.
It is expected that the School’s highly active role in research
training will be continued within the framework of the Drug
Research Academy, a research training programme targeted
at industry. Expected to be established in early 2002, the
Drug Research Academy is based on co-financing from nine
drug companies, the School and the Council on Research
Training (FUR). The last part of the funding package is ex-
pected to be in place shortly. In close interplay with industry,
the Drug Research Academy will provide the platform for
training 36 PhD students over a period of about six years.
THE RECTORS REPORT
PAGE 7
Margrethe
Vestager, then
Minister of
Education, dis-
played in-depth
knowledge and in-
terest in the School
during individual
meetings with stu-
dents, teachers
and management.
Spotlight on The Royal Danish School of Pharmacy
In the area of research training, the School has also earned
wide recognition from its appointment as a Marie Curie
Training Site, headed by Professor Sven Frøkjær. Winning this
appointment from the European Commission in sharp com-
petition with a number of other applicants will give the School
a distinctive European dimension in research training through
its hosting of a considerable number of European PhD re-
search fellows.
It is gratifying for the School to find its place in the land-
scape of Danish and international education and research.
This attention will encourage everyone at the School to do
their utmost to live up to the recognition. To underpin the sig-
nificance of the School’s role, Margrethe Vestager, then
Minister of Education, visited the School in September and
displayed in-depth knowledge and interest in the School
during individual meetings with students, teachers and man-
agement. It was a memorable day.
September 1st 2000 - January 31st 2001
In retrospect
ANNUAL REPORT 2000–2001
PAGE 8
September 2000: Two-hundred-and-three eager new phar-
macy students arrived to start their degree programme. Also
new were the 2000 Degree Regulations, which introduction
meant a complete restructuring of the pharmacology curricu-
lum, a new programme module in pharmacotherapy, a theory
of science course and the introduction of a bachelor’s degree
– which provides no professional qualification.
The beginning of the academic year also saw the opening of
the newly renovated student centre Alternativet. At the same
time, plans were presented for the conversion of Vivis Minde,
a facility previously used by the Department of Pharmaceutics
but earmarked for student use after conversion.
The environmental chemists at the Department of Analytical
and Pharmaceutical Chemistry and the Drug Delivery group at
the Department of Pharmaceutics had reason to be pleased.
A grant from the Apotekerfonden enabled the purchase of a
mass spectrometer. ‘We’ve had Volkswagen spectrometers
before, but this is a Rolls-Royce model!’ said Jette Tjørnelund
from the Department of Analytical and Pharmaceutical
Chemistry. The department will use the instrument to look for
drug remains in the environment while the Department of
Pharmaceutics will be investigating drug delivery of model
prodrugs in blood, among other things.
Steen Honoré Hansen, professor, DSc (pharm.) and head of
the Department of Analytical and Pharmaceutical Chemistry,
celebrated 25 years of public service. He has always played
an active role in the life of the School and continues to do so.
Tom Børsen Hansen, PhD student, was awarded first prize
for his work Science, general education and competence and
received DKK 40,000 from Margrethe Vestager, Minister of
Education.
In Plexus, Elise Rinvar, pharmacy student, argued for
greater specialisation within the pharmacy programme "to
better prepare the School to meet competition from new
emerging educations," as she puts it.
Dr Hans Lennernäs, professor, Uppsala University, was ap-
pointed assistant professor at the Department of Pharma-
ceutics. The association with an international figure will
strengthen the department’s pharmacokinetic research.
The month ended on a dramatic note when the area sur-
rounding the School was closed off and special forces called
in to arrest a man seen carrying a sawn-off shotgun in the
DSR student council rooms facing the University campus. Six
officers in bulletproof vests armed with pistols made the dis-
covery that the man was in fact a woman, and the gun was a
plastic replica bought for use at the annual initiation of new
students.
October 2000: Wild, wilder, wildest: revelry – student revelry
– reached such heights that Rector Birthe Jensen started get-
ting requests to ban student parties at the School. "I hope
everyone will do what they can to make sure this never be-
comes necessary," the rector urged, suggesting that the stu-
dents behave as though they were at home. "Then they might
treat the School’s property in the same way."
A survey among new students showed that they expect a
high degree of IT-based teaching. After graduating, 8% ex-
pect to find jobs in a community pharmacy while 63% count
on working in the pharmaceuticals industry. About 72% of
new students are female.
Programme director Else Lemmich was adamant that there
are no plans to specialise pharmacy education. "The pro-
gramme is well attuned to the broad job market where gradu-
ates will find work."
BITS AND PIECES
PAGE 9
In connection with Lægemiddeldagene 2000, pharmaceuti-
cal theme days, Verner Andersen, community pharmacist, (lic.
pharm.), was awarded The Danish Pharmaceutical Society’s
gold medal in recognition of his ‘Special contribution to
Danish pharmacy practice’.
Sven Erik Jørgensen from the Department of Analytical and
Pharmaceutical Chemistry was appointed research professor.
Kristian Strømgaard, assistant research professor at the
Department of Medicinal Chemistry, travelled to Slovenia to
receive the Krka Award 2000. The prize is awarded to
promising young scientists whose PhD work has made a sig-
nificant contribution to chemical and pharmaceutical re-
search. An impressive ceremony was staged for the presenta-
tion, which was transmitted by Slovenian TV.
November 2000: The natural product chemistry group at
the Department of Medicinal Chemistry has attracted new
young talent: Henrik Franzyk, chemical engineer, and Dan
Stærk, MSc and biochemist. Both in their thirties, the two
men will replace pharmacists Else and John Lemmich. "Now
that the pharmacy programme is so incredibly broad, we
have to have specialists to teach the individual subjects.
Pharmacists can’t teach everything as a matter of course.
NMR spectroscopy is one example," Dan Stærk points out.
Pharmacy student Jeppe Voss turned over chairmanship of
the student council, DSR, to Rasmus Engelbrecht.
Jørn Bo Sørensen, civil engineer, took up the appointment
of IT department head. "My first priority will be to get the net-
work functioning properly," he said.
Elections for posts on the collegiate bodies were held. DSR
chairman, Rasmus Engelbrecht, commented on voter turnout:
"Somewhere between an election to the church council and
the American presidential election."
December 2000: On Speech Day, Rector Birthe Jensen
explained that the ‘mass drain’ of pharmacists to the private
sector is the reason for the School’s difficulty in attracting and
retaining staff. "We should have transfer agreements like
sports clubs." On the same occasion, the students’ award for
‘Teacher of the Year’ was presented to Ole Jungersen, asso-
ciate professor, PhD, who at the time had already announced
his intention to retire.
At the request of students, the Department of Social
Pharmacy held a teaching day to discuss the communication
of requirements, objectives and methods for the department’s
teaching, as well as proposals to boost student motivation. "It
was a very inspiring form of evaluation," Jacob Grønne, phar-
macy student and member of the Study Board, concluded af-
terwards.
Povl Krogsgaard-Larsen, professor, DSc (pharm.), raised
the issue of whether the School is ready to meet the chal-
lenges of the pharmacy field in the post-genomic period. His
own response is that as a minimum the School must intro-
duce new academic disciplines and carry out reforms in tradi-
tional areas.
January 2001: The Royal Danish School of Pharmacy and
Pharmakon offered a new Specialisation in Community
Pharmacy programme. Nineteen community pharmacists are
enrolled in the new programme, which should be viewed as
an upgrade and further development of the professional quali-
fications of community pharmacists.
The School’s associate and assistant professors met to dis-
cuss recruitment and the problems of retaining present staff
members. The School’s academic staff pointed out that in-
creasing administrative burdens and vacancies means less
time for research. "We’ve reached the limit of what is accept-
able," was the general opinion.
Bjarke Ebert, one staff member who decided after several
years to leave the School for a job in the pharmaceutical in-
dustry, said the problem was not that staff decide to leave
their positions at the School. "That’s simply a fact of today’s
world. The real problem is the School’s inability to hire quali-
fied people to fill these vacancies when they arise."
Chairman of the PhD committee since 1993, Henning
Gjelstrup Kristensen, professor, DSc (pharm.), presided for
the last time over the proceedings at the annual Research
Day and handed over the reins to Erik Wind Hansen, associ-
ate professor, PhD. Research Day is the day on which the
School’s PhD students present the results of their research.
Jens Dencker Christensen, associate professor, PhD, re-
tired from the position of deputy rector, two years before the
expiry of the term. In consequence, the Senate (Konsistorium)
decided to abandon its former practice of electing a rector
and deputy rector for staggered terms, a decision originally
made to ensure continuity in the management of the School.
After the final deadline for nominations to the post of rector
of the School, it became clear that Povl Krogsgaard-Larsen,
professor, DSc (pharm.) would succeed Birthe Jensen, assis-
tant professor, DSc (pharm.), who has held the position since
1988.
An era of 40 years at the Royal Danish School of Pharmacy
finally came to an end: Alex Mehlsen Sørensen, assistant
professor, DSc (pharm.), retired. Programme director, head of
department and department board member are but a few of
the many offices he held over the years.
February 2001: "We must eliminate the issue of the
School’s future status as an independent institution from the
political agenda by offering dynamic, multi-facetted teaching,
research and research programmes," pronounced Povl
Krogsgaard-Larsen, professor, DSc (pharm.), who had a
couple of months yet to wait before taking up the office of
rector. "And we must market the School far more actively."
It was clear that the School’s two multidisciplinary centres,
NeuroScience PharmaBiotec and the Centre for Drug Design
and Transport, would be closed at the end of the year.
Despite positive evaluations and warm recommendations by
the Research Council, a political decision was made to close
down the centres owing to lack of funding.
Poul Kruse, assistant professor, DSc, and Niels Møller,
community pharmacist, PhD, published the seventh volume
of the work on the history of Danish pharmacies, De Danske
Apotekers Historie. A separate volume on a similar subject,
Apotekervæsenets historie i Danmark, was published. "I’ve
never been able to refer to any comprehensive works on
pharmacy and its many different perspectives. This book has
made that possible!" said Poul Kruse.
A new minisite on the School’s website was launched for
prospective students, who can find out all about the pharma-
cy programme and the main fields of pharmaceutical activity
at www.dfh.dk/farmaceut.
March 2001: Should the School offer educational opportu-
nities for postgraduates in subjects other than pharmacy?
What should a Bachelor’s programme contain? Do the
School’s research scientists have a duty to promote aware-
ness of pharmacists and their role in society? Do the two new
programmes at Århus and Odense pose a threat to the phar-
macy programme? Should the School be renamed The
Pharmaceutical University of Denmark? These were just some
of the compelling topics discussed at the student politics
weekend retreat.
Academic staff are not the only group tackling the problem of
recruiting and retaining personnel. Laboratory technicians face
the same dilemma. They are hoping a new pay agreement will
help attract suitable candidates to fill vacant positions.
Only about 130 people felt it worth their while to attend the
School’s open house event, 30% fewer than the previous
year, when a similar decrease on the year before had also
been noted. "The figures are very discouraging," said Ilse
Fjalland, head of the Study Division.
Mikael Ankersen, MSc, defended his doctoral dissertation
entitled Discovery of Peptidomimetic Growth Hormone
Secretagogoues.
April 2001: For the very last time, colleagues Birthe Jensen,
rector, and Jens Dencker Kristensen, deputy rector, chaired a
Senate meeting in these roles.
After four terms of election, it was time for Birthe Jensen,
assistant professor, DSc, to step down. She made this com-
ment about giving praise: “We’re not very good at showing
our appreciation of each other. I urge everyone to try and
make this a more important part of our everyday lives.” And
about the job of rector: “Challenging and exciting of course –
and occasionally frustrating. But never boring!”
None of the School’s research teams featured on the list of
those under consideration for funds granted by Større Tvær-
gående Forskerggrupper to major multidisciplinary research
teams. "There were no projects with a pharmaceutical objective
among the selected teams. This unfortunately reflects the fact
that pharmaceutical activities are only making a limited impact
on the state-based research system," was the disappointed
comment from Povl Krogsgaard-Larsen, professor, DSc.
For the second time, the School decided to advertise itself.
A full-page ad appeared in the youth magazine Chili, encour-
aging readers to get ‘high’ on pharmacy – a comment on an
article a month earlier in the same magazine under the head-
line: Get stoned at the pharmacy – it’s legal.
A survey about the services of the School’s pharmaceutical
library showed general satisfaction among students, whereas
researchers and PhD students did not feel the library met
ANNUAL REPORT 2000–2001
PAGE 10
their information needs. However, researchers were very sat-
isfied with other aspects of the library service.
May 2001: Bjarne Fjalland, associate professor, PhD, replaced
his title as head of department with that of deputy rector.
At the official reception held to mark Povl Krogsgaard-
Larsen’s appointment as rector, Børge Diderichsen, Director
of Corporate Research Affairs, Novo Nordisk, presented a gift
of DKK 250,000 – to the School’s PhD students.
Villy Dahl Jensen was appointed to head up the School’s
Budgeting and Accounting Division and gave the reassurance
that the School did not appear to be on the verge of
bankruptcy.
June 2001: The Senate (Konsistorium) discussed the pro-
posed departmental structure. With a political question mark
hanging over the future of the School, Povl Krogsgaard-
Larsen, rector, believes it is crucial for the School to signal to
the outside world that it is an institution that moves with the
times. Not all departments, however, are equally enthusiastic
about the new proposals, which include combining some de-
partments. "Explain the advantages of the new structure
first!" students demanded.
The School’s IT action plan was adopted. It proposed inten-
sive efforts in selected focus areas, which have been granted
DKK 500,000 in initial support.
The Teaching Committee assigned Merete Hende, MSc (en-
gineering), the job of mapping the type and extent of IT teach-
ing offered at the Royal Danish School of Pharmacy. The pro-
ject was expected to be completed by the end of the year.
Henning Gjelstrup Kristensen, professor, DSc (pharm.), took
over as chairman of The European Pharmacopoeia, which
contains the quality requirements with which all drugs dis-
tributed in Europe must comply.
July 2001: The Danish Association of Pharmacists, Section
D for pharmacy students, changed its name to Studenter-
netværket [The Student Network]. "We hope the new name
will conjure up an organization with a purpose," explained
board member Jacob Grønne. "And a common purpose and
identity are more important today than ever before," he point-
ed out.
Like all other state institutions, the Royal Danish School of
Pharmacy now has to pay rent for the government-owned
buildings it occupies. The School is therefore granted an ap-
propriation to finance the rent based on the value-added con-
cept, meaning the number of exams passed by students. The
intention is that institutions will economise on space when
they have to pay the cost of using it.
The front cover of the July issue of American Journal of
Physiology, Gastrointestinal and Liver Physiology featured a
picture created by Birger Brodin and Carsten Uhd Nielsen from
the Department of Pharmaceutics using their confocal laser-
scanning microscope. The accompanying article described
new aspects of how peptide transport can be regulated.
August 2001: The School’s new webmaster set himself the
task of making the School’s website more user friendly, dy-
namic and up to date.
Ole J. Bjerrum was made the School’s fourth professor of
pharmacology since the first appointment in the late 1960s. He
comes from a position as research advisor at Novo Nordisk.
At the graduation ceremony, the School noted that the past
academic year had produced 165 graduates, the largest
number ever in the School’s history. Women made up 70%.
After enrolling 194 new students, the School acknowledged
that for the first time it had been unable to fill its admission
quota of 200 places with new pharmacy students.
September 2001: The School was visited by a very well-pre-
pared Margrethe Vestager, Minister of Education. During her visit
she heard about student satisfaction with the programmes and
the School, while academic staff told her about the School’s vul-
nerable position when staff leave for jobs in the pharmaceuticals
industry, and management described the School’s close re-
search ties with industry. "Some people strike the right psycho-
logical chord with me. It’s far easier to help people who enjoy
their work than people who’re forever whining," said the minister
to the enthusiastic representatives of the School.
On the occasion of the publication of the book Eksamen –
eller hvad? [Exams – or what?] Arne Jacobsen, one of its au-
thors, gave examples from the School of how students can
pass an exam without understanding the material. One of his
main points was that the examination form can be an obstacle
to understanding.
The daily media highlighted plans put forward by Sonja
Mikkelsen, Social Democratic member of the Folketing,
Danish parliament, to set up pharmaceutical programmes in
BITS AND PIECES
PAGE 11
Odense and Århus. Both university cities were open to the
proposal.
The Royal Danish School of Pharmacy was appointed a
Marie Curie Training Site. "We are very pleased and proud,"
said Sven Frøkjær, professor, PhD, "because the nomination
is based on the high requirements expected of research insti-
tutions." The Marie Curie Training Sites are part of an EU
framework programme whose objective is to provide financial
support to enable PhD students to complete a study period
at selected research institutions in other EU countries as part
of their education.
The Research Centre for Quality in Medicine Use celebrated
its second birthday. "Although we aren’t a centre in the DKK
50 million class, there’s plenty going on at the centre," as-
sured the centre’s day-to-day manager, Professor Ebba
Holme Hansen.
October 2001: The School’s politically active students
staged a variety of activities aimed at generating greater stu-
dent interest in working on the collegiate bodies. "We need
more students to get involved in discussions and work for a
better School," said Rasmus Engelbrecht, chairman of the
DSR student council.
Surveys held among the School’s new students showed
that the prospect of employment in the public sector does
not hold wide appeal. Not one single student specifically in-
tends to find work in the public sector after graduation. The
outlook is slightly better for community pharmacies, where
7% aim to pursue their career. Top favourite is the pharma-
ceuticals industry, where 65% of the young students hope to
find jobs. At the same time, the survey showed that more
prospective students are using electronic rather than print
media to seek information about pharmacy education and
thus get an idea of the School and what it has to offer.
November 2001: The debate about modifying the depart-
mental structure was put on hold while the discussion about
focus areas in teaching and strategically important research
fields took pride of place. The disciplines of social pharmacy,
clinical pharmacy, pharmacotherapy and pharmacology were
pinpointed initially.
A new initiative teamed the Royal Danish School of Pharmacy
with the Royal Veterinary and Agricultural University to hold an
information day on the natural sciences for careers advisors
from Danish upper secondary schools. "It’s always nice to get
inside information that’s not available anywhere else," one ca-
reers advisor noted in the evaluation questionnaire.
The student body on the Study Board discussed ways of
getting the most out of an in-training period at a pharmacy.
The intention is not to accord lower priority to the profession-
al aspects of a pharmacist’s job but rather to put the time
available to better use.
Pharmacy student Anne Zimmermann replaced Rasmus
Engelbrecht as the DSR student council chairman.
December 2001: DSR’s prestigious teaching prize, Teacher
of the Year, went to Dan Stærk, assistant professor,
Department of Medicinal Chemistry. The DSR jury’s reason:
‘His well-structured, well-prepared approach.’
On Speech Day, Rector Povl Krogsgaard-Larsen said that
the goal of The Royal Danish School of Pharmacy was to meet
the need to produce an adequate number of qualified pharma-
cists at graduate and PhD level. Povl Krogsgaard-Larsen re-
jected the idea of setting up new pharmaceutical programmes
purely to solve the problem of the lack of pharmacists.
Pharmacy student Anne Zimmermann expressed the stu-
dents’ regret at the change of government. "We had just con-
vinced Margrethe Vestager [former Minister of Education] of
the way universities should be run."
Anders A. Jensen, assistant research professor at the
Department of Medicinal Chemistry, received the Danish
Academy of Natural Sciences PhD award for his dissertation
Molecular Pharmacology of Family C G-protein Coupled
Receptors.
Hans P. Merkle, professor of Galenical Pharmacy, Institute
of Pharmaceutical Sciences, Swiss Federal Institute of Tech-
nology Zurich, was appointed assigned professor at the
Department of Pharmaceutics.
The new student building was inaugurated with the antici-
pated festivity.
Mikael Begtrup, professor in organic chemistry, is the first
to receive the newly founded Carlsberg Prize for Research.
His commitment to teaching and maintaining young people’s
interest in chemistry, together with his own great interest in
passing on his knowledge, were some of the factors that led
to the award committee’s nomination of Mikael Begtrup.
The School’s new website was launched.
ANNUAL REPORT 2000–2001
PAGE 12
The School’s research journal, Lægemiddelforskning, was
published as usual, the only difference being that for the first
time it was issued without the annual report. Instead of fol-
lowing the academic year, it was decided to publish the an-
nual report for a calendar year in keeping with the financial
statement. The change means that the present report covers
the period from 1 September 2000 to 31 December 2001.
BITS AND PIECES
At the beginning of December 2001, the School’s website
underwent changes in both appearance and structure. The
facelift was a direct result of the School’s appointment of a
webmaster. The visual change represents only the first stage
of a longer process intended to expand and optimise the
School’s Internet-related activities and bring them up to date.
Webmaster Henrik Korzen is responsible for the daily run-
ning of the School’s website at www.dfh.dk and Intranet. He
will be ably assisted by Jesper Munck, information officer, as
well as the various departments of the School.
Since his appointment in August 2001, the webmaster’s pri-
mary tasks have included increasing the body of information
on site as well as modernising the layout and making it more
uniform.
December 2001 saw the launch of the new technologically
enhanced site, complete with new structure, new layout and
more information. One particularly welcome feature is the
opportunity to publicise more of the School’s many ongoing
activities.
Other initiatives to improve information levels and introduce
new services in the course of 2002 are already being planned
and prepared. These include electronic teacher-student com-
munication options, better electronic support for students
such as e-learning web pages and discussion fora.
The site structure will be made increasingly dynamic as a
basis for more flexible content and to facilitate the job of
maintaining and updating existing pages. The website will
also be better integrated with the School’s intranet.
One of our aims is to provide easier access to relevant infor-
mation, for instance, by making as much information as pos-
sible available in electronic form for School and external users
alike.
The process is already underway and in the years to come,
the appearance and structure of the School’s website will
gradually be modified in step with the need for an up-to-date
site that continually develops new services.
PAGE 13
New look for the School’s website
The Study Board covering the autumn term of 2000 and all of 2001
The Study Board is responsible for the administration and
development of the curriculum for the Master of Science de-
gree in pharmacy. Within the framework accepted by coun-
tries of the European Union, the Board adapts and develops
pharmaceutical studies to match employment opportunities in
the pharmaceutical sector.
In the period under review, the Study Board has had three
programme directors. Else Lemmich, associate professor at the
Department of Medical Chemistry, was programme director in
autumn 2000, followed by Peter Thygesen, associate profes-
sor, Department of Pharmacology in spring 2001. The under-
signed, Jette Jacobsen, associate professor, has been the pro-
gramme director of the Study Board since autumn 2001.
2000 DEGREE REGULATIONS
The first three terms governed by the 2000 Degree Regulations
were held for the first time in the period under review. Teach-
ing in the other terms in the period was carried out under the
framework of the 1997 Degree Regulations.
Under the 2000 Degree Regulations, the theory of science
module was held in the third term for the first time. The physi-
cal chemistry module was also carried out in a different form
for the first time. The module was previously taught over two
terms, but under the 2000 Degree Regulations is now taught
in its entirety in the third term. The head of the course and
participating students have evaluated the course on theory of
science and the Study Board is awaiting the results. The
Study Board wants related elements of the history of science,
theory of science and scientific methods to be incorporated
into the subjects taught in terms 4-8 under the 2000 Degree
Regulations, and for an elective course on the subject to be
offered as well. These course offerings supplemented by the
teaching already provided in the basic pharmacy course will
ensure a vertical core of teaching in the theory of science.
The Study Board has set up a Course Committee for the the-
ory of science module. The committee will be responsible for
ensuring that the course is held, evaluated and developed.
SUBJECT INTEGRATION
To increase subject integration and coordination between in-
dividual subjects and programme modules as well as to opti-
mise the study plan for the 2000 Degree Regulations and de-
velop the individual subjects, working groups either have
been or are still set up in the following subjects: pharmacog-
nosy, laboratory safety, toxicology, working environment and
statistics. In addition at the request of the Senate at the end
of the period under review, working groups were established
with management participation in physical chemistry and
pharmacotherapy, clinical pharmacy, pharmacology and social
pharmacy. The working group in pharmacognosy concluded
its work at the beginning of 2001 with suggestions for teach-
ing changes and new textbooks, which will be implemented
in the autumn term 2002. The working group in laboratory
safety drew up a compendium on laboratory safety at the
start of the autumn term 2001 for use in all laboratory training
courses in the first three terms. In autumn 2001 the working
group continued working on material concerning biological
safety in the laboratory. This material will be incorporated in
the compendium on safety in the laboratory, so that the com-
bined compendium can be used for all laboratory training
courses offered. The working group in toxicology and working
environment prepared a proposal for a subject description of
working environment. The subject description remains to be
finalised and further work is being done on proposals to coor-
dinate both major and minor elements of toxicology and the
working environment.
WEIGHT ON EVALUATION
In order to ensure the quality and development of the phar-
macy curriculum, the Study Board places great weight on
evaluation. Both single and repeated evaluations are carried
out and finalised in various ways. With regard to the 2000
ANNUAL REPORT 2000–2001
PAGE 14
Jette Jacobsen, Programme Director, Associate Professor, MSc (pharm.)
Degree Regulations, the Study Board has decided to evaluate
the following: new study modules, study modules subject to
radical changes and study modules that have been allocated
another place in the programme. Up to and including the pe-
riod under review the evaluation was undertaken by the
heads of the courses and participating students either in writ-
ing or orally. During the period under review, the Study Board
drew up a questionnaire for use in subsequent evaluations in
order to standardise the process.
Continuous and systematic evaluations are made at end-of-
term meetings held four times a year. Teachers, student re-
presentatives, heads of department, representatives from the
Study Board and representatives from Student Counselling
attend these meetings. The individual study modules are dis-
cussed in terms of teaching, teaching materials, placement in
the overall programme and coordination with other modules
in the same term.
NEW REQUIREMENTS
After repeated requests from several sides, including stu-
dents, the Senate finally adopted an Information and
Communications Technology (ICT) action plan in 2001.
The Teaching Committee under the Study Board works to
ensure development in teaching methods and to provide a ba-
sis for such development. For example a teaching day is held
every year for all teachers at the School. In the period under
review the topic for the day was ICT in teaching. The commit-
tee has held several mini-meetings for teachers about new
ways to teach and evaluate results. The Teaching Committee
works with the ICT Committee in order to introduce ICT in
teaching in the short term and thus the opportunity to change
the entire evaluation process in the longer term.
In 2001 the Study Board adopted requirements for report-
ing laboratory training in pharmaceutical formulation and pro-
duction, the project in pharmaceutical production, trainee pe-
riods at the pharmacy, alternative traineeships and elective
study modules. The background for the requirement is the
experience of the Study Board that many students apparently
manage to complete large segments of their course of study
– meaning that they carry out most or all of their laboratory
training – without having taken the theoretical part of the
module. When signing up for the study modules listed above,
students must have passed a specified number of obligatory
courses concluded by written examinations. The requirement
has been introduced to raise the level of what students get
out of the teaching and to ensure that the School expends its
resources on students with the right prerequisites.
Every year the Study Board ensures that there is a wide
and interesting selection of elective courses. This provides the
opportunity to quickly establish new courses in order to meet
current preferences both inside and outside the School. The
Study Board approves students’ applications for credit trans-
fer of electives from other institutions of higher education both
in Denmark and aboard. The Study Board registers and draws
up a list of all approved credit transfers so that other students
can consult it for inspiration.
THOUGHTS AND IDEAS WILL BE CONTINUED
At the end of 2001, cooperation with six other institutions of
further or higher education concerning DCN, Dansk Center
for Naturvidenskabsdidaktik (the Danish centre for didactics
and the natural sciences), was concluded, although the
thoughts and ideas behind it will be continued in order to
develop and improve teaching. One of the projects supported
by DCN and entitled "Testing examination forms directed at
understanding" is still ongoing. The aim of the project is to
study whether current teaching, particularly in conjunction
with laboratory training, is sufficiently directed at understand-
ing, as well as to study whether existing examination forms
adequately test the academic understanding of students with-
in pharmacy subjects. If the results are negative, there are
proposals for changes in both teaching and types of exami-
nations.
In 2001 the students on the Study Board initiated a vision-
ary debate that the new Study Board will continue in 2002.
In order to maintain the high number of pharmacy students
who graduate, we must continue to develop curriculum quality.
PAGE 15
ANNUAL REPORT 2000–2001
The Teaching Committee works with the ICT
Committee in order to introduce ICT in
teaching
Phamacotherapy – a new subject
Professor Helmer Ring Larsen
and Associate Professor Mette Rasmussen
The compulsory course in Pharmacotherapy is a joint venture
between the Department of Pharmacology and the Department
of Pharmaceutics. The course is an innovation as the teach-
ing is practically entirely clinical-problem based. It was intro-
duced in the fall term of 2000.
The aim of the course is to impact knowledge and insight
to the students in etiology, symp-
toms and clinical signs as well as
current therapy in the most im-
portant diseases with respect to
incidence and prevalence. How-
ever, the emphasis is laid upon
the rational use of drugs in gen-
eral and in the particular.
The course consists of introduc-
tory lectures, clinical case presen-
tations and workshops. During
the course the students are pre-
sented with ten clinical cases in
different disease categories in in-
ternal medicine, neurology and
psychiatry. The treatment options
and all aspects of therapy related
to the clinical case presentation is
worked on by the students in
study groups of 3 to 6 during a
one to two weeks period. The
cases are then discussed in a
two hours workshop with active
participation of ca. 50 students at
each session headed by one ex-
ANNUAL REPORT 2000–2001
PAGE 16
Central vein Hepatic vein
Portal triad
Central vein
Portal vein
Sublobular veinHepatic artery
Portal triads
CLEARANCE
STORAGE
HOMEOSTASIS
SECRETION
METABOLISM
FILTRATIONEXCRETION
SYNTHESIS
Portal triad
Bile duct
ternal and one internal teacher. In the workshop there is ample
time to evaluate the pharmacotherapy and to come up with
suggestions for treatment plans.
The course is finalized by a four hours written examination
consisting of four clinical cases of which the students have to
choose and answer three.
The clinical problembased teaching is executed by 4 inter-
nal teachers and 12 – 16 external lecturers, mainly special-
ized physicians from the Copenhagen University Hospital.
CaseHistory:
The patient is a 57 years old man with a previously heavy al-
cohol consumption and cigarette smoking for many years. He
has developed cirrhosis and chronic obstructive lung disease.
He is admitted because of fatigue, dizziness and tar-coloured
stools for two days. Because of previous bleeding from eso-
phageal varices, ascites and edema he is currently treated
with a non-selective beta-blocker and diuretics. He has been
sleeping during most of the day, while on the other hand he
has had difficulty sleeping at night because of nightmares. He
is complaining of cold fingers and toes as well as headache
and back pain. For his pain he receives paracetamol with
limited effect.
Examination:
On admission the patient is in a poor general and nutritional
condition, conscious but slow cerebrated. He has clinical signs
of cirrhosis, ascites and edema. Arterial blood pressure is
90/60 mm Hg, pulse 52 and temperature 37˚. Following trans-
fusion of four units of blood, the patient appears to be in a sta-
ble condition. Gastroscopy reveals a large ulcer in the duode-
nal bulb, covered with fibrin and without sign of actual bleed-
ing. Only small varices without signs of bleeding may be seen.
PAGE 17
Current treatment:
Tbl. Propranolol retard 160 mg q.d.
Tbl. Furosemide 40 mg b.i.d.
Tbl. Thiamine 300 mg q.d.
Tbl. Paracetamol 1 g t.i.d
Tbl. Ferro-duretter 1 b.i.d.
Lab. Analyses:
hemoglobin 4.1 (8.0 – 11.0 mmol/l). WBC 6.4 (3.0 – 9.0 billion/l), platelets 75 (150
– 400 billions/l), coagulation factors II,VII,X 0.65 (� 0.70), serum-albumin 31 (36.6
84.2 g/l), ALAT 95 (�50 u/l), serum-bilirubin 45 (4 – 22 �mol/l), serum creatinine
0.145 (0.060 – 0.130 mmol/l), serum sodium 128 (136 – 146 mmol/l), serum
potassium 2.5 (3.2 – 4.7 mmol/l), serum ferritin 400 (12 – 300 �mol/l).
Problems to be solved:
1. Explain how you are going to treat the patient’s duodenal
ulcer.
2. Discuss if a biopsy should be taken from this ulcer.
3. Indicate the cause of the tar-coloured stools (melaena).
4. Explain how you are going to optimise the diuretic therapy
and correct electrolytes.
5. Discuss if there is any medication, which ought to be
discontinued.
PHAMACOTHERAPY – A NEW SUBJECT
Management and Organisation
SCHOOL MANAGEMENT
The School is managed in accordance with the Danish
University Law which came into force on 1.1.93. This law
provides a framework within which more detailed regulations
are given by a statute – the present statute being passed in
1994. The School is run by a rector in collaboration with the
Senate (Konsistorium) and Study Board. Assisted by the
deputy rector, the rector is the School’s figurehead and
responsible for day-to-day management. For the period
covered by this report, the rectorate consisted of:
Rector, Professor, DSc (pharm.), Dr honoris causa Povl
Krogsgaard-Larsen
Deputy rector, Associate Professor, PhD (pharm.) Bjarne Fjalland
The rector’s and the deputy rector’s period of office expires 30.4.
2005. The rector and deputy rector are appointed for 4 years.
THE SENATE (KONSISTORIUM)
The Senate is the School’s leading organ. It is responsible for
the School’s interests as an education and research institution
and sets guidelines for long-term activities and development.
Proposals regarding alterations to the School statute have to
be approved first by the Senate and then by the Ministry of
Research. In addition, the Senate has to approve the School
budget. The Senate consists of the rector, who serves as
chairperson, and 14 members, 2 of whom are external and
appointed by Danmarks Forskningsråd (The Danish Research
Council), Forskningsrådenes Formandskollegium (The Chair-
men of the Research Councils) and Uddannelsesrådenes
Formandskollegium (The Chairmen of the Education
Councils).
ON 1. 2. 2002 THE SENATE CONSISTED OF THE FOLLOWING:
Chairperson:
Rector, Professor, DSc (pharm.), Dr honoris causa
Povl Krogsgaard-Larsen
External members:
Vice President, Anders Buur
Pharmacist, PhD (pharm.) Peter Lund Nielsen
Management representatives:
Deputy rector, Associate Professor, PhD (pharm.) Bjarne Fjalland
Head of Study, Associate Professor, PhD (pharm.) Tommy
Nørskov Johansen
Head of Department, Associate Professor, PhD (pharm.) Erik
Wind Hansen
Head of Department, Associate Professor, PhD (pharm.)
Margrethe Rømer Rassing
Head of Department, Professor, PhD. (scient.) Jerzy
Jaroszewski
Scientific staff representatives:
Associate Professor, PhD (pharm.) Bente Gammelgaard
Associate Professor, PhD (pharm.) Lona Christrup
Technical-administrative staff representatives:
Head of Secretariat, MSc (econ.) Henning Bo Nicolajsen
Chief Laboratory technician Ulla Geneser
Student representatives:
Thomas Høgh Jensen
Helle Poulsen
Behzad Ghorbani
ANNUAL REPORT 2000–2001
PAGE 18
Observers:
Administrator, MA Judith Christiansen
Head of Library Services Alice Nørhede
Head of Department, Associate Professor, MSc (pharm.)
Ebba Holme Hansen
Head of department, Prof., DSc. (pharm.) Steen Honoré Hansen
A series of committees have been established under the
Senate: The Library Committee, Information Committee, PhD
Committee, Stipendium Committee and Election Committee.
THE STUDY BOARD
The Study Board is responsible for the administration and
development of the curriculum for the Master of Science de-
gree in pharmacy. The Study Board consists of 50% scientific
staff and 50% Master of Science students. On 1. 2. 2002, the
Study Board consisted of:
Scientific staff representatives:
Associate Professor, PhD (pharm.) Tommy Nørskov Johansen
(Programme Director)
Associate Professor, PhD (pharm.) Erik Bechgaard
Associate Professor, PhD (pharm.) Ole Jøns
Associate Professor, PhD (pharm.) Søren Troels Christensen
Associate Professor, PhD (pharm.) Uffe Kristiansen
Student representatives:
Tove Kristiansen
Anne Estrup
Behzad Ghorbani
Eva L. Schmidt
Rasmus Engelbrecht
Observers:
Study Manager, MSc (pharm.) Ilse Fjalland.
SCHOOL ORGANISATION
The School’s five departments provide the framework for re-
search, teaching and related activities. Each department is
led by a head of department and a departmental board. The
departments comprise:
The Department of Analytical and Pharmaceutical Chemistry
The Department of Pharmacology
The Department of Pharmaceutics
The Department of Medicinal Chemistry
The Department of Social Pharmacy
A principal co-operation committee and safety committee
have been established for the entire School. Local co-operation
committees have been elected in four of the departments and
in the Administration Department. The School’s Administration
Department is run by the Administrator, whose areas of work
and responsibility are defined by the Rector. The administra-
tion is divided into the secretariat, course administration and
guidance, finance department, higher education administra-
tion system (VUE), IT department, technical services and
building administration.
MANAGEMENT AND ORGANISATION
PAGE 19
RECTORATE
STUDY BOARD
DEPARTMENT OF
ANALYTICAL AND
PHARMACEUTICAL
CHEMISTRY
DEPARTMENT OF
PHARMACOLOGY
DEPARTMENT OF
PHARMACEUTICS
DEPARTMENT OF
MEDICINAL
CHEMISTRY
DEPARTMENT OF
SOCIAL PHARMACY
ADVISORY COMMITTEEPHD COMMITTEE
FIVE DEPARTMENTS LIBRARY
ADMINISTRATION
SAFETY COMMITTEEPRINCIPAL
CO-OPERATION
COMMITTEE
Organisation 2001
SENATE
ANNUAL REPORT 2000–2001
Financial Statement 2001
The complete 2001 financial statement for The Royal Danish
School of Pharmacy is available in Danish only. For copies
please contact the finance department at The Royal Danish
School of Pharmacy or our website www.dfh.dk
STAFF
The Royal Danish School of Pharmacy employs staff to un-
dertake teaching and research, run the library and handle the
operation of buildings, administration and other tasks. In
2001 the number of full-time scientific staff was 190.6 -sever-
al of whom are PhD students and scientific staff hired on a
temporary basis - a slight reduction compared to 2000, when
the number was 194.3. The reduction is largely due to tem-
porary vacancies in permanent positions.
ANNUAL REPORT 2000–2001
PAGE 20
Type of scientific staff 2001 (total 201,5 full-time employees).
The scientific staff includes professors, associate professors, assistant professors, PhD students etc.
The part-time staff includes external associate professors, teaching assistants etc.
The technical and administrative staff includes laboratory workers, office workers, technicians etc.
The diagram shows The Royal Danish School of Pharmacy gives high priority to educa-
ting PhD students. The aim is to fulfil the industrial need for good scientists and The
Royal Danish School of Pharmacy’s need for a new generation of scientists to replace
the scientific employees who plan to retire over the next 5-10 years.
Staff employees (full-time)
2000 2001 2002 Budget
Scient. Part-time Technical Total Scient. Part-time Technical Total Scient. Part-time Technical Totalstaff and adm. staff staff staff and adm. staff and adm. staff
staff staff
Teaching 47.7 11.5 79.3 138.5 52.1 10.6 75.6 138.3 52.6 10.1 75.3 138.0
Research 145.6 0.6 37.5 183.7 137.5 0.3 35.3 173.1 148.6 1.0 36.4 186.0
Fundamental (state) 81.1 0.3 13.9 95.3 76.0 0.2 13.3 89.5 81.0 0.5 14.0 95.5
State/priv. Subsidies 53.6 7.6 61.2 51.0 6.6 57.6 54.0 7.0 61.0
PhD education 0.6 0.4 1.0 0.3 0.8 1.1 0.6 0.4 1.0
Contarct work 10.3 0.3 15.6 26.2 10.2 0.1 14.6 24.9 13.0 0.5 15.0 28.5
Library 7.3 7.3 7.7 7.7 8.0 8.0
Buildings 11.4 11.4 8.0 8.0 8.0 8.0
Administration 1.0 17.2 18.2 1.0 18.8 19.8 1.0 18.0 19.0
Others 1.0 1.0 2.3 2.3 3.0 3.0
Other building expenditure 0.0 3.9 3.9 4.0 4.0
Total 194.3 12.1 153.7 360.1 190.6 10.9 151.6 353.1 202.2 11.1 152.7 366.0
FINANCIAL STATEMENT 2001
Total expenditure rose from DKK 178.4 million to DKK 214.3
million, primarily due to the new practice of paying rent for
our buildings. The rental costs of DKK 30.5 million are can-
celled out by rental income of DKK 31.5 million.
Research costs fell by DKK 3.9 million to DKK 85.8 million.
The reduction is in the grant-funded area, which had extraor-
dinarily high expenses in 2000 due to a change in accounting
principles. Thus the reduction in costs does not represent a
reduction in research activities.
Research income derives from several financial sources.
The table ”Revenues for research work” shows that the bulk
of income derives from the state appropriation for basic re-
search. Research revenues have risen from DKK 82.6 million
to DKK 98.0 million, or an increase of DKK 15.4 million. Again
the increase is tied to the change in accounting principles
adopted in 2000, which resulted in extraordinarily low rev-
enues for that year. The increase in the basic government ap-
F INACIAL STATEMENT
PAGE 21
Expenditure (DKK million)
2000 2001
Education 50.106 51.722
Fundamental research 42.295 44.162
Research activitities funded by state and private subsidies 34.585 28.733
Contract research work 0.580 0.907
PhD education 12.268 12.034
Research work total 89.728 85.836
Library 4.512 4.491
Building expenditure 15.574 15.453
Administration 8.755 9.827
Other 1.224 1.501
Common expenses total 25.553 26.781
Tax on real property 2.528 33.119
Other building expenditure 2.997 7.085
Other expenditure total 5.525 40.204
Internal expenditure 3.012 5.251
Total expenditure 178.436 214.285
Revenue for research work (DKK million)
2000 2001
State appropriation for fundamental research 48.300 55.700
State subsidies 13.264 19.180
EU + other international foundations 0.266 0.814
Other foundations 14.424 16.584
Contract research revenue 1.207 0.819
PhD education 5.100 4.900
Total revenue for research work 82.561 97.997
Financial result 2001 (DKK million – years price)
2000 2001 2002
Fin. Statement Fin. Statement Budget
Expenditures
Wages and salary 117.2 120.9 132.8
Other expenses 61.2 93.4 80.1
178.4 214.3 212.9
Revenues
The State Budget net 77.2 111.6 83.9
Other revenues 87.7 108.3 129.0
164.9 219.9 212.9
Result -13.5 5.6 0.0
Result ordinary activity 0.9 5.6 0.0
Result external activity -14.4 0.0 0.0
Total -13.5 5.6 0.0
Accumulated surplus in years prices (DKK million – years price)
2000 2001 2002
Fin. Statement Fin. Statement Budget
Transfer from previous years - ordinary 20.5 21.4 27.0
Transfer from previous years - external 14.4 0.0 0.0
34.9 21.4 27.0
Result this year - ordinary 0.9 5.6 0.0
Result this year - external -14.4 0.0 0.0
-13.5 5.6 0.0
Transfer to next year - ordinary 21.4 27.0 27.0
Transfer to next year - external 0.0 0.0 0.0
21.4 27.0 27.0
propriation for research is connected to a multi-year agreement with
the Ministry of Science, Technology and Innovation, as well as the
incorporation of the Royal Danish School of Pharmacy’s ”Centre for
Drug Design and Transport”.
The Royal Danish School of Pharmacy’s financial performance for
2001 is shown in the table ”Financial results 2001”. An operating
surplus of DKK 5.6 million accrues to a total of DKK 27 million to be
transferred and used to implement strategic objectives in the years
ahead. However, it has not yet been decided whether we will be al-
lowed to keep it all. Special approval from the Ministry of Finance is
required.
Students
MASTER OF SCIENCE (MSC) STUDIES
Since 1994 the number of students enrolled annually has in-
creased to about 200. Figure 1 shows how many students
were enrolled at the School during the period 1991-2001.
The number indicates how many new students were enrolled
as of 1 October in the year of enrolment. The average age of
students enrolled as of 1 September 2001 was 21.9.
For the first time in many years the School has been unable
to fill its admission quota. Thus as of 1 October 2001 only
186 students were enrolled. The reduction in enrolments is
due to a 35% decline in the number of applicants to pharma-
ceutical studies over the past three years. Thus since spring
2001 the School has significantly heightened its focus on re-
cruitment, including promoting the School’s image to its pri-
mary target group of potential applicants, which is graduates
of upper secondary school interested in chemistry and biology.
The majority of the students are admitted 0-2 years after
graduation. This is seen as highly satisfactory and appropriate
for educations based on the natural sciences.
As a result of the increase in enrolments since 1994, the
School’s total student population has also risen significantly
from 925 students in 1991 to 1102 students in 2001. The
student population is counted on 1 October and figure 2
shows the population for the period 1991-2001.
The School’s production of MSc pharmacy graduates is
shown in figure 3. The production of graduate pharmacists
ANNUAL REPORT 2000–2001
PAGE 22
Enrrolled Students 1991-2001
(as of 1 October in the year of enrolment)
Student Population 1991-2001
(as of 1 October in the year of enrolment)
Number of MSc graduates 1990/91-2000/01
Fig. 1 Fig. 3
Fig. 2
STUDENTS
Single course students on the MSc-programme 1991/92-2000/01
Merit Students
Year 91/92 92/93 93/94 94/95 95/96 96/97 97/98 98/99 99/00 00/01
Number of students 29 10 19 34 70 106 132 147 140 86
Number of course-places 37 14 22 47 125 159 175 171 172 112
Open Education scheme
Year 91/92 92/93 93/94 94/95 95/96 96/97 97/98 98/99 99/00 00/01
Number of students 33 40 76 48 22 28 23 58 40 31
Number of course-places 39 51 105 82 35 51 43 68 49 42
has increased in step with the increased admission of new
students. In future we expect an average production of 150-
160 MSc graduates annually, corresponding to a completion
rate of 75-80%. This is considered highly satisfactory in com-
parison with other types of university studies. In the academic
year 2000/2001 the School produced 165 graduates, the
largest number of MSc pharmacy graduates in the history of
the School. The pharmaceutical job market desperately
needs MSc and PhD graduates in pharmacy, and thus offers
excellent job prospects for both groups.
The average age of MSc pharmacy graduates in 2000/01
was 26.8, which also indicates that the average study period
continues to be low: 5.9 years. 76 % of graduates earned
their MSc degree in six years or less, which is considered
highly satisfactory.
SINGLE COURSE STUDENTS
The School offers students wishing to take single courses
two enrolment options, either as “merit students” (from other
institutions of higher education), or under the “open education
scheme” with partial user payment. The School has required
partial payment since the autumn term of 1995. The School’s
selection of single courses covers all subjects – both compul-
sory and elective – under the Master of Science in pharmacy
programme.
The table shows the development in number of single
course students enrolled in the period 1991/92 - 2000/01.
The considerable reduction in number of merit students in
2000/2001 relative to previous years is due to a special
agreement with the University of Copenhagen that ran from
1996/1997 to 1999/2000. The special agreement allowed
physical education students from the University to enrol in our
basic course on statistics. If we disregard the effect of the
special agreement, there has been no significant difference in
the number of single course students in recent years.
PAGE 23
ANNUAL REPORT 2000–2001
About half of the single course students are enrolled in accor-
dance with cooperation agreements with the Faculty of
Science of the University of Copenhagen and the Royal
Veterinary and Agricultural University concerning the two-year
MSc course in environmental chemistry. The other single
course students follow a very wide spectrum of our compul-
sory and elective subjects.
INTERNATIONAL STUDENT EXCHANGE
There are wide variations in European health care systems,
which also differ from the American and Australia systems, for
example. Similarly, pharmacy education also varies from
country to country. Ongoing discussions focus on the oppor-
tunities to promote greater uniformity in education, particularly
within Europe, and we are looking at how pharmacists are
put to use in other countries, and what we can learn from
that. Student exchanges are one of the ways we can con-
tribute to constructive and well-founded discussion on the
subject. The School is an eager participant in debate and
supports student exchange.
One of the areas that reflect the School’s commitment to
student exchange is funding. The School spent a total of DKK
250,000 in financing foreign travel, corresponding to approx.
DKK 10,000 per student. Other sources of foreign travel fi-
nancing are the EU Commission’s Socrates/Erasmus pro-
gramme in the amount of approx. DKK 40,000 and the
Scandinavian Nordplus in the amount of approx. DKK
20,000. These funds are returned if students do not utilise
the exchange agreements.
In 2001 student exchanges took place in the following
parts of the world:
During the exchange the majority of students, both those
studying abroad and visiting students, work on their theses,
which are often based on projects carried out in laboratories.
At present the School offers only one course in English,
International Health Care. We have many enquiries from for-
eign students about taking courses here, but the language
barrier often rules out the opportunity for students to visit for
the purpose of taking classes. Students writing theses, how-
ever, can often manage with English, which is spoken by ad-
visors and most people in the laboratories.
Students whose travel has been subsidised by the School
are required to fill in a questionnaire at the end of their stay
abroad. Without exception, they always highly recommend
foreign study to their fellow students. Any other advice they
might have on the basis of their experiences abroad is
passed on to the international office of the School and thus to
other students. A corresponding questionnaire for students
visiting us is being prepared.
PAGE 24
Country Number of Number ofstudents abroad visiting students
Europe 8 6
USA 7 0
Australia 7 0
Other 2 2
STUDENTS
PAGE 25
Research Centres at The Royal Danish School of Pharmacy
NEUROSCIENCE PHARMABIOTEC CENTRE
The NeuroScience PharmaBiotec Centre comprises three sub-
centres, two of which are coordinated by project managers
from H. Lundbeck A/S and NeuroSearch A/S. The third sub-
centre consists exclusively of academic research groups and
is coordinated by the School of Pharmacy. The Centre is
managed overall by the School of Pharmacy.
The aim of the research projects is to produce results that
the pharmaceutical industry may transform into drug develop-
ment projects. The academic research teams do not, how-
ever, target their efforts towards development projects or
problems specific to the industry. Their aim is high level inter-
national research. Results considered to have special poten-
tial are patented and
subsequently published.
It is increasingly acknow-
ledged that only results
of high scientific caliber
push the boundaries of
modern science and
provide value in this
context. Both academia
and the pharmaceutical
industry are aware that
there is no special bene-
fit in university scientists
setting out to solve spe-
cific developmental pro-
blems.
Research scientists
from academic institu-
tions and the pharmaceutical industry share the job of super-
vising PhD students, most of whom spend an internship
period of varying length in industrial laboratories. The next
generation of research scientists will, as far as possible, be
trained to make a solid contribution to innovative pharmaceu-
tical research in partnership with other academic groups.
Although the Neuroscience PharmaBiotec Centre was posi-
tively evaluated by an international panel of experts the Centre
was terminated by political decision at the end of 2001.
CENTRE FOR DRUG DESIGN AND TRANSPORT
The "Centre for Drug Design and Transport" is an extramural
research centre established in November 1997 as a four-year
programme and therefore terminated in October 2001. The
centre is based on seven Danish research groups and funded
by the Danish Medical Research Council, several Danish
pharmaceutical companies and the participating academic in-
stitutions. Professor Sven Frøkjær is the head of the centre.
The Royal Danish School of Pharmacy was granted additional
funding due to a positive evaluation by international referees. In
theory the additional funds will allow the most promising activities
of the centre to be continued for up to another four-year period.
The overall objective of the "Centre for Drug Design and
Transport" has been to study new principles for the design
and transport of drug substances. The goal is pursued by a
highly integrated collaboration between scientists specialised
in different disciplines related to drug research and develop-
ment. The centre covers the follow areas: organic chemistry,
medicinal chemistry, membrane biophysics, drug delivery
pharmacology and clinical research. The participating part-
ners are The Royal Danish School of Pharmacy, Technical
ANNUAL REPORT 2000–2001
University of Denmark, PET Centre, Aarhus University
Hospital, Centre for Imaging Diagnostics and Medico-tech-
nique, State University Hospital, Department of Dermatology,
University Hospital, Gentofte, and Alpharma A/S, H.Lundbeck
A/S, Leo Pharmaceutical Products A/S, NeuroSearch A/S,
Novo Nordisk A/S and Nycomed Pharma A/S.
The education and training of pharmaceutical scientists in a
thoroughly interdisciplinary manner is a major activity of the
centre and involves scientists from both academia and industry.
FKL – THE RESEARCH CENTRE FOR
QUALITY IN MEDICINE USE
The Research Centre for Quality in Medicine Use (FKL –
Forskningscenter for Kvalitetssikret Lægemiddelanvendelse)
was established in 1999. The overall objectives of the pro-
jects are to provide scientific evidence to optimise the profes-
sionals’ pharmacotherapy and the population’s medicine use.
Hereby, the research contributes to improved public health
and quality of life as well as improved economy of the individ-
ual and the society.
To achieve the Centre’s objectives, the approach has to be
multidisciplinary, inter-professional and trans-institutional. The
researchers involved in the Centre’s activities represent sever-
al disciplines including clinical pharmacy, epidemiology, gen-
eral practice, health economics, health policy, public health,
social pharmacy and sociology. Groups from the following
academic and public institutions participate in the Centre:
Pharmakon, the Danish College of Pharmacy Practice, the
County of Vestsjælland, the County of Funen, Copenhagen
County, the National Institute of Public Health, Copenhagen
University, the University of South Denmark, Aalborg Univer-
sity, the University Hospitals Centre for Nursing and Care
Research (UCSF), the Institute of Rational Pharmacotherapy
and NEPI – the Swedish Network for Pharmacoepidemiology.
The Centre is managed by the School of Pharmacy and di-
rected by Professor Ebba Holme Hansen of the Department
of Social Pharmacy.
The Centre for Quality in Medicine Use embraces a range of
projects. The major share of the Centre’s resources has been
allocated to projects about pharmacy practice. The Pharmacy-
University Study has broken new grounds by establishing an
action research triangle which unites community pharmacists,
pharmacy students and researchers in an effort to uncover
medicine related problems and information needs of patients
suffering from angina pectoris, asthma and diabetes. Another
pharmacy practice project is focusing on self-care and self-
medication. After piloting, this project has reached the inter-
vention phase.
Another group of Centre studies analyses the Danish popu-
lation’s medicine use through data obtained from question-
naire based surveys of large representative samples of ado-
lescents and adults.
Macroperspectives on medicine supply is a thematic area
looking into e.g. deregulation of the pharmacy sector and the
views of different interested parties. The new medicine con-
sumer is an innovative substudy analysing the users’ per-
spectives in relation to global consumer trends.
Further centre projects deal with the user’s perspective on
medicine use. Under this umbrella a Danish team is coordi-
nating a strong international multidisciplinary research group.
Much interest in Danish health care is devoted to the quality
of physicians’ prescribing.
The FKL-centre carries out qualitative and quantitative
analyses to establish a research foundation for interventions
into GPs’ prescribing.
The 1991 Pharmacy
Foundation has been
the major external
sponsor of the Centre’s
activities, but funding is
also provided by the
Foundation for Finan-
cing Research in Gen-
eral Practice and in the
Health Service (The
Research Foundation),
the Health Insurance
Fund, the Danish Medi-
cal Research Council’s
Regional Fund for
Eastern Denmark and
various private funds.
NEUROSCIENCE PHARMABIOTEC CENTRE
PhD degree programme
The Danish PhD degree is a three-year programme compris-
ing a research project, courses at PhD level, teaching and
communication activities, an independent PhD thesis and
subsequent defence. It is customary for PhD students to inte-
grate a three to six month study visit to a research institute
outside The Royal Danish School of Pharmacy during the
course of the degree programme, preferably abroad.
As of 1 October 2001, a total of 131 students were enrolled
at the school. The distribution by gender was relatively con-
stant in 2000/2001, 1999/2000 and 1998/1999, i.e. 49%
women and 51% men. We find this gender distribution satis-
factory.
The age of PhD students at the time of enrolment varies
slightly. In 2000/2001, the average age at the time of enrol-
ment was 29.2 years; 27.6 years for the PhD students em-
ployed at the School. Among the enrolled PhD students,
pharmacists account for about 60%, chemists and biologists
23% and engineers 8%. About 8% of the PhD students hold
a MSc degree from abroad.
The School provides financial support to 56 of the 131 PhD
students, in part through its own scholarships and in part
through co-financed scholarships. The majority of the PhD
students are fully or partly funded by external co-operators.
There is a great need for PhDs in industry and thus also for
external funding.
ANNUAL REPORT 2000–2001
Degree 1996/97 1997/98 1998/99 1999/00 2000/01
Pharmacist 67% 66% 64% 56% 60%
Chemist/biologists 15% 15% 22% 24% 23%
Engineers 4% 8% 2% 9% 8%
Abroad 12% 9% 6% 7% 8%
Age when enrolled
Enrolments
Number of PhD students enrolled
PAGE 28
The 131 PhD students are enrolled as follows:
21 (16%) at the Department of Analytical and
Pharmaceutical Chemistry
23 (18%) at the Department of Pharmacology
35 (27%) at the Department of Pharmaceutics
43 (33%) at the Department of Medicinal Chemistry
9 (7%) at the Department of Social Pharmacy.
From 1 October 2000 to 30 September 2001, PhD degrees
were conferred on 29 PhD students. In addition, one person
registered in 2000/2001 for assessment without matriculation.
The students were enrolled for 3 years and 11 months on av-
erage, a decrease compared to 1998/99 and 1999/00. This
development is satisfactory as the enrolment period is count-
ed from the first day of enrolment to the day the PhD degree
is conferred. The average duration of enrolment is affected by
maternity leave, for one, but other unknown factors may con-
tribute as well.
The majority of the PhD graduates from the School are em-
ployed by the pharmaceutical industry, many even before
their PhD degree is conferred.
PHD COURSES
From 1 September 2000 to 31 December 2001 the school
taught 18 courses specifically intended for PhD students.
PHD TRAINING
PhD degrees conferred
Length of enrolment
PAGE 29
Participants were primarily PhD students from the School and
other Danish universities and young scientists from the phar-
maceutical industry. Efforts are made to increase the interna-
tional participation in the PhD courses, as well as the Danish
participation in PhD courses taught by partners in the interna-
tional ULLA collaboration.
ULLA SUMMER SCHOOL
The fifth ULLA Summer School was held in London in August
2001. The summer school is organised every other year by
the ULLA collaboration consisting of the Faculty of Pharmacy
(University of Uppsala), the School of Pharmacy (University
of London), Leiden/Amsterdam Centre for Drug Research
(University of Leiden and Vrije Universiteit Amsterdam), the
Faculty of Pharmacy (University of Paris South), and The
Royal Danish School of Pharmacy.
A total of 124 PhD students and young scientists from in-
dustry participated in the summer school in London, 26 of
them PhD students from the School. Teachers from ULLA in-
stitutions also participated, nine of them from Copenhagen.
The ten-day summer school offered 32 courses, each lasting
from one to two days. Posters by participants were accessi-
ble throughout the Summer School.
A symposium was organised on “Non-Viral Gene Delivery”.
RESEARCH DAY
Every year the PhD Study Board organises a Research Day in
order to give PhD students the opportunity to make an oral
presentation or present a poster about their research project.
Research Day was held on 12 January in 2001. Professor
David Ganderton from the University of Bath was the guest
speaker.
NEW MINISTERIAL ORDER ON THE PHD DEGREE
In 1999 the PhD programme in Denmark was evaluated by
the Danish Research Council. The final evaluation report was
discussed by the PhD Study Board, which found recommen-
dations made in the evaluation well in keeping with the
School’s current policies. The report has given rise to a dis-
cussion about the strategic goals of the pharmaceutical PhD
programme, in particular with regard to the international di-
mension.
In June 2001 the PhD Study Board discussed the draft of a
new ministerial order on the PhD programme and the PhD
degree. We are waiting for the new ministerial order from the
Ministry.
PAGE 30
Graduate School of Drug ResearchThe research training school, Graduate School of Drug
Research, was established in September 1998 on the basis
of a 5-year grant from the Danish Research Academy. The
aim of the Graduate School is to train the next generation of
drug researchers. Emphasis is placed on integrated research
training with the aim of performing innovative drug research in
an interdisciplinary and highly integrated research environ-
ment. The industrial perspective of drug research is essential
to the study program. The Graduate School was at the es-
tablishment primarily based on the activities of two research
centres, The NeuroScience Centre (1997-2001) and The
Centre for Drug Design and Transport (1997-2001), although
participation is open to all PhD students who meet the
school's requirements.
From December 1998 to August 2001, The Graduate
School initiated 17 PhD studentships co-financed by the
Royal Danish School of Pharmacy, The Danish Research
Academy and the pharmaceutical industry. The Graduate
School grants financial support to PhD courses at the School
of Pharmacy to ensure the participation of leading internatio-
nal scientists as lecturers.
The Graduate School has been involved in the organization
and hosting of a series of mini-symposia, often in collaboration
with the above-mentioned research centres or scientific asso-
ciations. During the period January-December 2001 the Gra-
duate School of Drug Research organized 7 mini-symposia.
All of these symposium arrangements were widely announced
and were attended not only by PhD students enrolled at the
Graduate School but also by a number of other PhD students
and scientists from both academia and the drug industry. One
of these mini-symposia was organized as a two-day arrange-
ment at Sorø Storkro with Dr. Wolfgang Froestl, Novartis
Pharma AG, Basel as the keynote speaker. All of the mini-
symposia organized at the Royal Danish School of Pharmacy
were also very well attended, and in agreement with the over-
all goal of the Graduate School, these arrangements are in-
creasingly attracting junior scientists from Northern Germany
and from the other Scandinavian countries. This international
interest probably reflects that most of the speakers at the
symposia are international recognized scientists. Titles of the
mini-symposia organized at the Royal Danish School of
Pharmacy were "Applied Heterocyclic Chemistry", "Receptor
Structure and Function", "ADME in Drug Research", "Drug
Design Copenhagen 2001", "Reactive Drug Metabolites -
their formation, reactions, and the toxicological conse-
PHD DEGREES FROM 1 SEPTEMBER 2000
TO 30 SEPTEMBER 2001
Jens Buchardt
PhD Thesis: A Solid Phase Combinatorial Approach
to Phosphinic Peptide Inhibitors of Matrix Metallo-
proteinases.
Supervisors: Associate Professor Per Vedsø,
Department of Medicinal Chemistry, Professor
Morten Meldal, Carlsberg Laboratory and Dr Niels
Tækker Foged, Carlsberg Laboratory
Enrolled at Department of Medicinal Chemistry.
Karin Löwenstein Christensen
PhD Thesis: Design of Redispersible Dry Emulsions.
A Potential Oral Drug Delivery System.
Supervisors: Professor Henning Gjelstrup Kristensen,
Department of Pharmaceutics and PhD Gitte
Pommergaard Pedersen, Leo Pharmaceutical
Products
Enrolled at Department of Pharmaceutics.
Gerda Marie Friedrichsen
PhD Thesis: Peptide-Coupled Compounds Targeted
for the Oligopeptide Transporter. Synthesis and Bio-
logical Evaluation.
Supervisors: Professor Mikael Begtrup, Department
of Medicinal Chemistry, Associate Professor Per
Vedsø, Department of Medicinal Chemistry, Asso-
ciate Professor Bente Steffansen, Department of
Pharmaceutics and MSc Palle Jakobsen, Novo
Nordisk A/S
Enrolled at Department of Medicinal Chemistry.
Patrick Garibay
PhD Thesis: The Combinatorial Synthesis of Possible
Insulin Mimetics.
Supervisors: Associate Professor Per Vedsø,
Department of Medicinal Chemistry, Professor Mikael
Begtrup, Department of Medicinal Chemistry and
Chemist Thomas Høeg-Jensen, Novo Nordisk A/S
Enrolled at Department of Medicinal Chemistry.
Thomas Groth
PhD Thesis: Methodology for Solid Phase Combi-
natorial Synthesis of Novel Peptide Isosteres and
Mimetics Derived from N-Terminal Peptide Aldehydes.
Supervisors: Associate Professor Per Vedsø,
Department of Medicinal Chemisty and Professor
Morten Meldal, Carlsberg Laboratory
Enrolled at Department of Medicinal Chemistry.
Steen Gyldenkærne
PhD Thesis: Risk Assessment of Pesticides in Agri-
cultural Fields with Special Emphasis on Carabids
and Staphylinids.
Supervisors: Associate Professor Sven Erik
Jørgensen, Department of Analytical and Pharma-
ceutical Chemistry, Associate Professor Bent Halling-
Sørensen, Department of Analytical and Pharma-
ceutical Chemistry and Research Manager Jørgen
Jacobsen, The Danish Institute of Agricultural
Sciences
Enrolled at Department of Analytical and
Pharmaceutical Chemistry.
ANNUAL REPORT 2000–2001
All of the mini-symposia or-
ganized at The Royal Danish
School of Pharmacy were
very well attended.
quences" and "From Receptor to Prescription in Clinical
Neuropsychiatry".
Dr. Sonata Krikstolaityte, Kaunus University, Latvia spent a
6-month period at the Graduate School working on a project
focusing on the conversion of wasp polyamine toxins into
pharmacological tools and potential drugs. During this re-
search stay Professor Algirdas Sackus, Kaunus University,
Latvia visited the Graduate School as a guest scientist a
number of times. Dr Mogens Nielsen was associated with the
Graduate School for a number of months. Mogens Nielsen
played a key role in the organization of one of the PhD cours-
es "In Vivo Neuropharmacology" and was involved in the
planning of the PhD course "Cellular Pharmacology and
PAGE 31
Toxicology". In addition, he organized and carried through a
very well attended study circle on fluorescence technologies
in pharmacological and biomedical research.
A number of internationally recognized scientists visited the
Graduate School as guest lecturers, notably Professor Leo
Hösli, University of Basel and Vice President, Dr Claus
Bræstrup, H. Lundbeck A/S.
Based on two major grants to the Graduate School of Drug
Research from Novo Nordisk A/S, the Graduate School was
in a position to grant 3 PhD's, who had completed very suc-
cessful PhD projects, Novo Nordisk PhD Plus Prizes. One of
the prize recipients also received the PhD Prize of the Danish
Academy of Natural Sciences.
PHD TRAINING
Tina Weinkauf Hahn
PhD Thesis: Acetainophen (paracetamol). – Pharma-
cokinetics and Analgesic Effect in Postoperative
Patients.
Supervisors: Associate Professor Mette Rasmussen,
Department of Pharmaceutics, Associate Professor
Janne Rømsing, Department of Pharmaceutics and
Dr.med. Steen W. Henneberg, Rigshospitalet and
Research scientist Helle Angelo, Bispebjerg Hospital
Enrolled at Department of Pharmaceutics.
Birgit Sehested Hansen
PhD Thesis: Characterisation of in vitro Growth
Hormone Release Stimulated by Growth Hormone
Releasing Hormone and Growth Hormone
Secretagougues.
Supervisors: None.
Enrolled at as an independent student.
Henrik Hegnbo Hansen
PhD Thesis: The Impact of Brain Injury: Involvement
of the System of Endocannabinoid Ligands and Re-
ceptors.
Supervisors: Associate Professor Harald S. Hansen,
Department of Pharmacology and Professor Steen
Honoré Hansen, Department of Analytical and Phar-
maceutical Chemistry
Enrolled at Department of Pharmacology.
Anders Asbjørn Jensen
PhD Thesis: Molecular Pharmacology of Family C
G-Protein Coupled Receptors.
Supervisors: Professor Povl Krogsgaard-Larsen,
Department of Medicinal Chemistry, Research
Scientist Hans Bräuner-Osborne, Department of
Medicinal Chemistry and Head of department
Christian Thomsen, H. Lundbeck A/S
Enrolled at Department of Medicinal Chemistry.
Anette Gemal Jensen
PhD Thesis: Quality Assessment of Herbal Re-
medies. Focus on Phytopharmaceuticals Containing
Hypericum perforatum L. and Ginkgo biloba L.
Supervisors: Professor Steen Honoré Hansen,
Department of Analytical and Pharmaceutical Chemi-
stry, Associate Professor Lene Gudiksen, Department
of Medicinal Chemistry, and Head of Department
Elsebet Østergaard Nielsen, NeuroSearch A/S
Enrolled at Department of Analytical and
Pharmaceutical Chemistry.
Mads Skak Jensen
PhD Thesis: Cyanide Toxicology – Insights into
Mechanisms of Action and Antidotal Strategies.
Supervisors: Associate Professor Erling Sonnich
Thomsen, Department of Analytical and
Pharmaceutical Chemistry and
Professor Niels C.B. Nyborg, Novo Nordisk A/S
Enrolled at Department of Analytical and
Pharmaceutical Chemistry.
Simon Bjerregaard Jensen
PhD Thesis: Parenteral Water-in-Oil Emulsions as
Sustained Release Systems for Hydrophilic Com-
pounds.
Supervisor: Professor Sven Frøkjær, Department of
Pharmaceutics, Associate Professor Charlotte
Vermehren, Department of Pharmaceutics and Dr
Ingrid Söderberg, Leeds University
Enrolled at Department of Pharmaceutics.
Pia Knudsen
PhD Thesis: The Experience of Younger Women with
SSRI Antidepressants – a User Perspective.
Supervisors: Professor Ebba Holme Hansen,
Department of Social Pharmacy and Associate
Professor Janine Morgall, Department of Social
Pharmacy
Enrolled at Department of Social Pharmacy.
Hasse Kromann
PhD Thesis: Glutamate Receptor Ligands: Synthesis
and Pharmacological Characterization.
Supervisors: Professor Povl Krogsgaard-Larsen,
Department of Medicinal Chemistry, PhD Frank A.
Sløk, NeuroSearch A/S and Associate Professor
Tommy N. Johansen, Department of Medicinal
Chemistry
Enrolled at Department of Medicinal Chemistry.
Iben Larsson
PhD Thesis: Comminution of Particulate Solids in a
Micros Ring Mill.
Supervisors: Professor Henning Gjelstrup Kristensen,
Department of Pharmaceutics and Associate Pro-
fessor Jørn Møller-Sonnergaard
Enrolled at Department of Pharmaceutics.
Karsten Lindhardt
PhD Thesis: Nasal Drug Delivery.
Supervisors: Associate Professor Erik Bechgaard,
Department of Pharmaceutics, Professor Sveinbjörn
Gizurarson, Iceland University, Head of Department
Hanne Wulff Nielsen, Nycomed Pharma A/S and
Head of Department Erik Didriksen, Leo Pharma-
ceutical Products
Enrolled at Department of Pharmaceutics.
Hans-Christian Holten Lützhøft
PhD Thesis: Environmental Risk Assessment of
Antimicrobials.
Supervisors: Associate Professor Sven Erik
Jørgensen, Department of Analytical and Pharma-
ceutical Chemistry and Associate Professor Bent
Halling-Sørensen, Department of Analytical and
Pharmceutical Chemistry
Enrolled at Department of Analytical and
Pharmaceutical Chemistry.
Rasmus Worm Mortensen
PhD Thesis: Reactive Drug Metabolites.
Supervisors: Professor Steen Honoré Hansen,
Department of Analytical and Pharmaceutical Che-
mistry, Associate Professor Jette Tjørnelund, Depart-
ment of Analytical and Pharmaceutical Chemistry,
Associate Professor Claus Cornett, Department of
Analytical and Pharmaceutical Chemistry and PhD
Ulla Grove Sidelmann, Novo Nordisk A/S
Enrolled at Department of Analytical and
Pharmaceutical Chemistry.
Addmore Ndekha
PhD Thesis: Strengthening Community Participation
in Schistosomiasis Control: Lessons from the Guruve
District (Zimbabwe) Schistosomiasis Control Programme
Using Phytolacca Dodecandra (a Plant Molluscicide).
Supervisors: Professor Ebba Holme Hansen,
Department of Social Pharmacy, Dr. Godfrey Woelk,
University of Zimbabwe, Associate Professor Per
Mølgaard, Department of Medicinal Chemistry and
Senior Advisor Peter Furu, Danish Bilharziasis Labo-
ratory Enrolled at Department of Social Pharmacy.
Annette Sams Nielsen
PhD Thesis: Characterisation of CGRP Induced
Effects in Human and Guinea Pig Cerebral Arteris.
Chasing Functional Receptor Heterogeneity.
Supervisors: Associate Professor Inger Jansen-
Olesen, Department of Pharmacology and Professor
Jan Engberg, Department of Pharmacology
Enrolled at Department of Pharmacology.
Carsten Uhd Nielsen
PhD Thesis: Intestinal Peptide Transporter Mediated
Drug Delivery Using Stabilized Dipeptide Pro-Moities.
Affinity, Transport, Drug Release and Regulation.
Supervisors: Associate Professor Bente Steffansen,
Department of Pharmaceutics, Professor Sven
Frøkjær, Department of Pharmaceutics, Research
Associate Professor Birger Brodin Larsen, Depart-
ment of Pharmaceutics and Chemist Mitchell E.
Taub, Novo Nordisk A/S
Enrolled at Department of Pharmaceutics.
PAGE 32
Attentive listeners at the Research Day 2001.
ANNUAL REPORT 2000–2001
Pernille Bondeskov Nielsen
PhD Thesis: Tocopherol as an Oral Drug Delivery
System.
Supervisors: Professor Henning Gjelstrup Kristensen,
Department of Pharmaceutics, Associate Professor
Anette Müllertz, Department of Pharmaceutics and
Thomas Norling, Dumex-Alpharma
Enrolled at Department of Pharmaceutics.
Peter Aadal Nielsen
PhD Thesis: Strongly Polar Molecules in Aqueous
Solution Studied by NMR and Computational
Chemistry.
Supervisors: Professor Tommy Liljefors, Department
of Medicinal Chemistry, Professor Jerzy Jaroszewski,
Department of Medicinal Chemistry, Associate
Professor Per-Ola Norrby, Department of Medicinal
Chemistry and Head of Department Klaus
Gundertofte, H. Lundbeck A/S
Enrolled at Department of Medicinal Chemistry.
Torben Rasmussen
PhD Thesis: Molecular Modeling of Assymetric
Catalysts.
Supervisors: Associate Professor Per-Ola Norrby,
Department of Medicinal Chemistry, and Professor
Mikael Begtrup, Department of Medicinal Chemistry
Enrolled at Department of Medicinal Chemistry.
Anette Graven Sams
PhD Thesis: Solid Phase Aldol and Diels - Alder
Reactions in the Formation of Novel Peptide Isosters
as Putative Protease Inhibitors.
Supervisors: Professor Povl Krogsgaard-Larsen,
Department of Medicinal Chemistry and Professor
Morten Meldal, Carlsberg Laboratory.
Enrolled at Department of Medicinal Chemistry.
Majid Sheyhkzade
PhD Thesis: Characterisation of Calcitonin Gene-
Related Peptide Receptor Subtypes and Function in
Rat Coronary Arteries.
Supervisors: Professor Niels C. Berg Nyborg, Novo
Nordisk A/S
Enrolled at Department of Pharmacology.
Ulrik Sidenius
PhD Thesis: Purification and Analysis of
Selenoprotein P from Human Plasma.
Supervisors: Associate Professor Bente
Gammelgaard, Department of Analytical and
Pharmaceutical Chemistry, Associate Professor Ole
Jøns, Department of Analytical and Pharmaceutical
Chemistry and Professor Ole Farver, Department of
Analytical and Pharmceutical Chemisty
Enrolled at Department of Analytical and
Pharmceutical Chemistry.
Gitte Elgaard Terp
PhD Thesis: Molecular Modeling of Matrix Metal-
loproteinases and Their Inhibitors – A New Concept
for Ligand Selection and Prediction of Binding
Affinities.
Supervisors: Associate Professor Flemming Steen
Jørgensen, Department of Medicinal Chemistry and
Chemist Inge Thøger Christensen, Novo Nordisk A/S
Enrolled at Department of Medicinal Chemistry.
Daniel Brunicardi Timmermann
PhD Thesis: Subcellular Localization and Pharma-
cological Characterization of Voltage Gated Calcium
Channels in Cultured Neocortical Neurons.
Supervisors: Professor Arne Schousboe, Department
of Pharmacology, Associate Professor Uffe
Kristiansen, Department of Pharmacology
Enrolled at Department of Pharmacology.
Marianne Willert
PhD Thesis: A Combinatorial Library Approach to the
Identification of Protease Substrates and Inhibitors.
Supervisors: Professor Povl Krogsgaard-Larsen,
Department of Medicinal Chemistry and Professor
Morten Meldal, Carlsberg Laboratory
Enrolled at Department of Medicinal Chemistry.
Niels Hønberg Zangenberg
PhD Thesis: A Dynamic in vitro Lipolysis Model.
Supervisors: Professor Henning Gjelstrup Kristensen,
Department of Pharmaceutics, Associate Professor
Anette Müllertz, Department of Pharmaceutics and
Managing Director Lars Hovgaard, Galenica Aps
Enrolled at Department of Pharmaceutics.
PHD TRAINING
PAGE 33
Evaluation of the oral presentations at the Research Day 2001. Former PhD study Administrator Eva Horn Møller, the
new Chairman of the PhD Committee Erik Wind Hansen and the former Chairman Henning Gjelstrup Kristensen. Both
Erik Wind Hansen and Henning Gjelstrup Kristensen have been members of the PhD Committee since 1993.
Specialisation inCommunity Pharmacy
Head of the Study Board for Specialisation in Community
Pharmacy, Associate Professor, Poul R. Kruse, DSc (pharm)
The educational scope of The Royal Danish School of Phar-
macy is not restricted to the curriculum for the MSc degree in
Pharmacy and PhD programmes. The School also sees it as
its duty to provide further and continuing education program-
mes for pharmacists, including those working in community
pharmacies. The School has therefore been actively involved
in developing systematic continuing education for community
pharmacists ever since programmes were introduced in 1966.
Similarly, the School is represented on the Advisory Committee
on Pharmaceutical Training, EU, one of whose aims is further
education for community pharmacists. The School is keen to
help promote the use of pharmaceutical knowledge through-
out the health care sector.
Recent years’ recommendations by EU and WHO advisory
committees on pharmaceutical training have prompted dis-
cussions along these lines between the School and profes-
sional authorities and organisations, including Pharmakon a/s,
which runs the established pharmaceutical continuing educa-
tion programme. In this connection, the question of the need
for specialisation in community pharmacy was raised. As a
result of these talks, representatives from the Department of
Social Pharmacy and Pharmakon a/s prepared a proposal for
regulations for a specialised programme that complies with
the recommendations of the EU’s advisory committee. The
professional authorities and organisations expressed their
support for the proposal during subsequent discussions.
It was against this background that the Senate of The Royal
Danish School of Pharmacy decided in April 2000 to intro-
duce a specialised programme in community pharmacy at the
School, in cooperation with Pharmakon a/s and to appoint a
study board for the new programme with representatives from
all sectors of the pharmaceutical profession. In June 2000,
Apotekerfonden af 1991 provided a grant to develop the
specialised programme and establish a secretariat, making it
possible to launch the programme on 1 January 2001.
The specialised programme is intended for community phar-
macists with at least two years’ working experience. Based
on the pharmacist’s professional knowledge and practical ex-
perience, the programme aims to supplement pharmacists’
pharmacological, managerial and personal qualifications. On
completion of the programme, the School issues a certificate
documenting the qualifications gained. The programme is
therefore an opportunity for community pharmacists to devel-
op and gain accreditation for specialist skills acquired through-
out their career, regardless of whether their goal is to be a
pharmacy manager with responsibility for the professional
development of others or a community pharmacist.
The specialised programme in community pharmacy consists
of the following main subjects:
1. Pharmacotherapy and symptom assessment, including
anatomy, physiology, pharmacology, pharmacokinetics,
symptomatology and pathology.
2. Pharmacy practice: Performance and development of the
pharmacy’s professional services based on WHO’s Guidelines
on Good Pharmacy Practice (GPP), including:
• Prescription medications for individuals: distribution, in-
formation to patients and ensuring results (pharmaceuti-
cal care)
PAGE 34
ANNUAL REPORT 2000–2001
• Personal care and symptom assessment
• Disease prevention and health promotion
• Rational medication consumption.
3. Social pharmacy: Disease-, medication- and health-related
behaviour, healthcare economy, pharmacoepidemiology and
management of medication consumption.
4. Healthcare advice and information, including methods for
advising individuals, informing target groups, and general
instruction.
5. Documentation and information, including quality devel-
opment, evaluation and surveys of pharmacy practice;
use of pharmaceutical information systems and information
technology.
6. Pharmacy operations, including management, skills devel-
opment, organisation, operations and economy.
The specialised programme has a standard duration of one
working year, corresponding to 60 European Credit Transfer
System points (ECTS points). Pharmacists attend the pro-
gramme, which runs over a minimum of two and a maximum
of six years, alongside their regular community pharmacy job.
The programme consists of the following elements:
• Compulsory courses (12 points)
• Elective courses (minimum 12 points)
• Literature study (maximum 5 points)
• Study trip (maximum 5 points)
• Dissertation (minimum 15 points).
The compulsory courses comprise an introduction and four
subject courses. The four subjects are:
1. Healthcare theory, including the pharmacy profession,
community health, the consumer’s perspective and medi-
cation consumption.
2. Documentation in pharmacy practice, including planning,
performing and evaluating surveys, framework conditions,
theories and methods.
3. Pharmacy practice management, including management
and organisation, Human Resource Manage-ment, busi-
ness development and pharmacy operations.
4. Professional advice and information, understanding con-
sumers’ perspectives and expectations, framework conditions
and methods.
A secretariat has been set up at the School for the specialised
programme in community pharmacy. As well as providing study
guidance, the secretariat will assist during the programme’s in-
troductory phases and ensure that it develops satisfactorily in
terms of practical running and academic content. An adminis-
trator has been appointed to be in charge of secretariat ser-
vices, and a formal co-operation has been set up between the
secretariat and the School’s new specialised programme in hos-
pital pharmacy.
Nineteen pharmacists applied in the first admission round for
the specialised programme in community pharmacy starting
on 1 January 2001. An introductory course was held for them
in April 2001, and the first subject course, Healthcare theory,
was held in August and November 2001. Ten pharmacists
applied for the second admission round for the programme
starting on 1 January 2002.
The Study Board for Specialisation in Community Pharmacy
has prepared a final proposal for the programme’s regulations
and planned the entire programme course, as described in
The Study Guide to the Specialist Programme in Community
Pharmacy. The study board submitted the programme regula-
tions to the Senate, which approved them in November 2001.
At the same time, in accordance with The Development
PHD TRAINING
PAGE 35
Poul R. Kruse: Introducing a specialised programme in community pharmacy.
Contract 2000-2003 between the School and the Ministry of
Education, the Senate adopted a motion for the School to
initiate negotiations with the Ministry as soon as possible to
ANNUAL REPORT 2000–2001
Hanne Herborg (Head of Research and
Development, Pharmakon) teaches at the new
Specialisation in Community Pharmacy.
approve the specialised programme in community pharmacy
for inclusion in a relevant module of the further and continuing
education system for adults.
The introduction of the specialised pro-
gramme in community pharmacy has at-
tracted broad interest and backing from all
interested parties, as evidenced by several
references to the programme in pharmacy
journals in 2000 and 2001. It has been par-
ticularly satisfying for the School to note that
all the pharmacy profession’s authorities and
organisations have nominated representa-
tives to the study board.
The members of The Study Board for Specialisation in Community Pharmacy:
Poul R. Kruse, Associate Professor, DSc (pharm), Department of Social Pharmacy, nominated by The Royal Danish
School of Pharmacy (chairman)*
Bente Steffansen, Associate Professor, PhD (from 1 September 2001 Associate Professor Janne Rømsing, PhD),
Department of Pharmaceutics, nominated by The Royal Danish School of Pharmacy*
Peter Thygesen, Associate Professor, PhD (from 1 February 2001 Helmer Ring, Professor and Consultant, Doctor of
Medicine), Department of Pharmacology, nominated by The Royal Danish School of Pharmacy*
Kurt Fonnesbæk Rasmussen, Director, MSc (pharm), nominated by Pharmakon a/s*
Kirsten Pultz, project coordinator, MSc (pharm), nominated by Pharmakon a/s*
Susanne Trøck-Nielsen, proprietor pharmacist, nominated by the Danish Pharmaceutical Association
Majken Juul Jensen, pharmacist, nominated by the Danish Association of Pharmacists, of which she is chairman
Bodil Strøh, proprietor pharmacist, nominated by The Danish Pharmaceutical Society
Lars Arboe Harild, examiner (from 1 September 2001, Anne-Marie Vangsted, Head of Division, MSc [pharm]), nominated
by the Danish Medicines Agency
Mikala Vasehus Holck, pharmacist, nominated by participants in the specialised programme for community pharmacists
* Indicates members of the executive committee of the study board
Head of Secretariat: Trine Hopp, MSc (pharm), (from 1 June 2001, Thomas Clemens Jensen, MSc (pharm)), Department
of Social Pharmacy, The Royal Danish School of Pharmacy.
PAGE 36
ANNUAL REPORT 2000–2001
PAGE 37
Department of Analytical and Pharmaceutical Chemistry
Research at the Department of Analytical and Pharma-
ceutical Chemistry covers the following main areas: analyti-
cal chemistry (involving environmental and bioinorganic chem-
istry as well as chemical toxicology (aimed at accidents with
hazardous chemicals)) and pharmaceutical chemistry (applied
physical chemistry).
RESEARCH
ANALYTICAL CHEMISTRY
Basic research in separation science
The research in analytical chemistry is devoted to basic re-
search in separation science as well as to research in drug
metabolism involving the development of new analytical meth-
ods. The development of new analytical methods is based in
part on basic research. The research in separation science fo-
cuses on separation mechanisms in high-performance liquid
chromatography (HPLC) and capillary electrophoreses (CE).
This research is currently being expanded to cover hyphenat-
ed techniques like HPLC-mass spectrometry (HPLC-MS), CE-
(MS), HPLC-nuclear magnetic resonance (HPLC-NMR) and
eventually CE-NMR.
Spectrometry - especially NMR - is an important part of the
research area, and the potential of using NMR in bioanalytical
chemistry is explored.
A major area of application is drug metabolism, where a
number of drugs are under investigation. The interaction of
reactive metabolites (e.g. glucuronides) with biopolymers is
also studied and structure activity relationships investigated.
Part of the research is conducted in collaboration with other
research groups at the School, at hospital laboratories and in
the pharmaceutical industry.
Research in analytical chemistry also covers determination
of trace elements and their biotransformations. The main in-
terest here is developing new methods of speciation analysis.
The analytical techniques are ion chromatography with chemi-
luminescence detection, graphite furnance atomic absorption
spectrometry and ICP-MS in combination with HPLC and CE.
Supervisors:
Steen Honoré Hansen, professor, Dsc (pharm)
Inga Bjørnsdottir, associate professor, PhD (until September
2000)
Claus Cornett, associate professor, PhD
Bente Gammelgaard, associate professor, PhD
Ole Jøns, associate professor, PhD
Alex Mehlsen Sørensen, associate professor, PhD (until
January 2001)
Jette Tjørnelund, associate professor, PhD (until September
2001)
ANNUAL REPORT 2000–2001
PAGE 38
Head of Department Professor Steen Honoré Hansen, DSc
DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY
ENVIRONMENTAL CHEMISTRY
Chemical environmental research focuses on the emission of
elements and compounds to the internal or external environ-
ment, and on their processing and effects on these environ-
ments. Environmental chemistry integrates environmental risk
assessment, toxicology, chemistry and applied analytical
chemistry. Current research projects deal with the modelling
of effects of emissions on aquatic ecosystems, effect and
speciation of heavy metals, risk and effect analysis of
medicine, and the relationship between environment and
health and endocrine disruption by xenobiotics, incl. drugs.
Supervisors:
Sven Erik Jørgensen, associate professor, Dsc (Eng)
Bent Halling-Sørensen, associate professor, PhD
Søren Nors Nielsen, external associate professor, PhD
(until June 2001)
ENVIRONMENTAL RISK ASSESSMENT
OF PHARMACEUTICALS
Antibiotics are used widely across Europe to treat farm animals.
Once released into the environment, the pharmaceuticals
and their metabolites may persist and have the potential to
runoff to surface waters or leach to groundwater where they
can impact human and environmental health. Unlike other
classes of substances (e.g. pesticides, metals and nutrients),
the environmental fate of veterinary pharmaceuticals is poorly
BIOINORGANIC CHEMISTRY
The importance of inorganic chemistry in biology, especially
metal ion coordination chemistry, has gained considerable ap-
preciation during the last decade. The discovery of the roles
of metal ions and metalloproteins in health and disease
through genetic and biochemical studies has drawn the at-
tention of molecular and cell biologists in increasing numbers.
Indeed, there are few areas of modern biology where inorgan-
ic chemistry is not destined to make its mark. Thus, inorganic
chemistry combined with molecular biology and protein che-
mistry in studies of metal protein interactions will influence the
thinking and research activities of chemists and biologists in
the future. A little appreciated fact is that the brain is a spe-
cialised organ that concentrates metal ions. So, combining in-
organic chemistry with molecular biology and protein chem-
istry in order to study abnormal metal protein interactions will
undoubtedly lead to a better understanding of the molecular
origin of major neurological diseases.
The overall purpose of our research is to continue and fur-
ther develop studies of the relationship between metal ions
and macromolecules experimentally as well as theoretically, a
field entitled bioinorganic chemistry on the border between in-
organic chemistry and biology. Our collaboration with leading
research groups in other countries, including powerful bio-
technological centres, ensures a continuous integration with
international frontline research in bioinorganic chemistry.
Supervisor:
Ole Farver, professor, DSc
understood. A three-year project is therefore being conducted
involving modelling, laboratory, semi-field and field studies.
The aim of the study is to identify those factors and process-
es affecting the fate of veterinary pharmaceuticals in order to
adapt existing risk assessment models or develop new mod-
els. Laboratory studies will investigate sorption, degradability
and ecotoxicity of a range of veterinary pharmaceuticals. A
range of new analytical methods, LC-MS-MS in particular, will
have to be developed for the purpose.
The results of these studies will be used to assess the
models currently available and, where appropriate, the mod-
els will be adapted to cope with pharmaceuticals. A range of
scenarios will be developed to assess the risk of veterinary
pharmaceuticals.
Supervisors:
Flemming Ingerslev, Anne Marie Jacobsen, Ann-Louise
Steinicke-Larsen, Anne Lykkeberg, Jette Tjørnelund and Bent
Halling-Sørensen together with several international research
groups
Hormonally active agents in the environment
Over the past ten years, it has appeared that a number of en-
vironmental contaminants are able to provoke adverse
changes in endocrine systems in humans and in the environ-
ment. The research within this area has primarily focused on
the development of a test aimed at screening the endocrine
effects of chemicals on the crustacean Acartia Tonsa. At pre-
sent an assay for testing endocrine effects on breast-cancer
cells, the E-screen method, is under development.
The analytical chemical aspects have been put more in fo-
cus in a recently started project. Methods to preconcentrate
surface water are being developed, and analytical methods
(HPLC-MS-MS) and the previously mentioned bioassays are
used in the search for an overall picture of the oestrogen po-
tential of surface waters.
Supervisors:
Henrik Rasmus Andersen, Søren Nors Nielsen, Flemming
Ingerslev and Bent Halling-Sørensen together with the
Technical University of Denmark
CHEMICAL TOXICOLOGY
Based on the simultaneous use of toxicology and chemistry,
information on hazardous substances and accidents involving
such substances has been made available to public authori-
ties, the medical community and others. Several of these in-
quiries have resulted in toxicological investigations. Two main
research branches have appeared: inhalation toxicology (pul-
monary edema, toxic smoke from fires, criteria for evacuation,
etc.) and clinical toxicology (hospital reception and treatment
of patients suffering from the effects of chemical accidents,
antidote preparedness, etc.). Thus the Department functions
as a centre of knowledge on the use of hazardous sub-
stances and accidents involving such substances.
Supervisor:
E. Sonnich Thomsen, associate professor, PhD
PHARMACEUTICAL CHEMISTRY
The pharmaceutical chemistry research programme relates to
optimisation of drug formulation involving prodrug design and
salt formation. Aspects of drug delivery under investigation
encompass factors influencing bioavailability and duration of
drug action. Current research may be divided into four areas
that are more or less interrelated (i) “Manipulation of drug sol-
ubility through prodrug design and salt formation” including
both aqueous and lipid solubility, (ii) “Parenteral depot formu-
lations” with the focus on oil solutions and crystal suspen-
sions, (iii) “Prodrugs - identification of transport groups ex-
hibiting a biological functionality” where we have initiated a
search to identify suitable chemical compounds with signifi-
cant affinity to blood components, and (iiii) “Facilitation of
biomembrane drug transport by prodrug design. Furthermore,
the pharmaceutical chemistry group is engaged in pharma-
ceutical chemical profiling of drug substances including as-
sessment of drug stability. Our research is partly conducted in
collaboration with both internal and external groups.
Supervisors:
Claus Selch Larsen, professor, PhD DSc (pharm)
Helle Brøndsted, associate professor, PhD
Gitte Juel Friis, associate professor, PhD (until December
2000)
Karin Fredholt, associate professor, PhD (until October 2000)
Flemming Madsen, associate professor, PhD (until September
2000)
Søren Nors Nielsen, associate professor, PhD (from June
2001)
Kirsten Eberth, associate professor, PhD
DONATIONS AND GRANTS
Ole Farver gratefully acknowledges support from the Danish
Natural Science Research Council; the Danish Medical
Research Council; the Lundbeck Foundation and the
Novo-Nordisk Foundation.
Bent Halling-Sørensen has together with senior researcher,
PhD Lars Bogø Jensen, SVS received each DKK 375.000 per
year for a two year period (2001-02) from SJVF (Statens
Jordbrugsvidenskabelige Forskningsråd) to the project:
ANNUAL REPORT 2000–2001
PAGE 40
“Assessment of the fate and resistance development of se-
lected antibiotic metabolites in soil” grant no. 53-00-0279.
Bent Halling-Sørensen and Jette Tjørnelund have received
DKK 4.0 mio from The EU 5th frame programme (project
period 2000-03): Environmental risk assessment of veteri-
nary medicines in sludge (ERAVSMIS). Project no. EESD-
ENV-99-1, EVK1-1999-00034P, for a three year project
Claus Selch Larsen and Helle Brøndsted have received DKK
680.000 from Centre for Drug Design and Transport.
Bent Halling-Sørensen has from the Danish Environmental
Agency received DKK 500.000 for the project ”Drugs and the
environment” projects no. 00-650-24.
Steen Honoré Hansen received DKK 300.000 from the
Danish Medical Research Council for partly financing of a
micro HPLC equipment.
Svend Erik Jørgensens current supported projects are:
Enreca Project with Dar es Salaam University prolonged to
August/September 2003 – DKK 4,3 million and EU-supported
project, coordinator Sovan Lek, Toulouse University, EURO
118.000.
GUESTS
PhD Dina Tawfik Mohammed El-Sherbiny from Mansoura
(Egypt). September-December 2000.
Dr Stig Pedersen from University of Oslo, Norway. October 2000.
Nuria Vives I Llácer from Barcelona, Spain. September-
December 2001.
Dr. Michael G. Rowan from University of Bath, UK. June-
August 2001.
Dr. Paul Blackwell from Cranfied University, England, visited
the environmental chemistry group in February 2001 in order
to work on the development of an analytical method to be
used in a common research project financed by the EU.
PhD student Jianhua Wang, Technical University of Denmark
(1.10.00-30.11.00)
Hu Weiping from Nanjing Institute of Limnology and
Geography, Chinese Academy of Science. Year 2000 Fall.
Santanu Ray, Post.doc. from Calcutta University , January -
April 2001.
Sixtus Kayombo from Dar es Salaam University, August -
November 2001.
ARRANGEMENTS
The Environmental chemistry group arranged (30.7.–10.8.
2001) the course ”Environmental risk assessment of pharma-
ceuticals and chemicals” as part of ”The Øresund Summer
University 2001”. 25 students from 12 different countries par-
ticipated in the course.
PRESENTATIONS
Halling-Sørensen B. Biologically active substances in society
and their environmental fate. Apoteket AB symposium “Vad
vet vi om läkemedel i miljön?” in Stockholm, Sweden (Invited
speaker) 7 June 2001.
Halling-Sørensen B. Occurrence and environmental properties
of antibiotics used in Denmark. Presented at the SETAC
conference Organic soil contaminants 2-5 September 2001 at
Eigtved Parkhus, Copenhagen Denmark.
Hansen SH. “Challenging the principles of setting limits in
pharmacopoeial tests”. The Future Face of the European
Pharmacopoeia Nice, 8-9 February 2001 (Invited lecturer).
Hansen SH. “Hyphenation of CE to ICP-MS and to nano-
spray MS for high sensitivity and selectivity in biomedical
analysis”.14th International Bioanalytical Forum, 3-6 July 2001
at the University of Surrey, Guildford, UK (Invited plenary lec-
turer).
Hansen SH. “The use of microemulsion electrokinetic chro-
matography (MEEKC) and dynamically coated capillaries for
drug analysis by capillary electrophoresis”. 11th International
Symposium on Advances and Applications of Chroma-
tography in Industry. Bratislava, Slovak Republic, 27-31
August 2001 (Invited lecturer).
Hansen SH. “The use of microemulsion electrokinetic chro-
matography (MEEKC) and dynamically coated capillaries for
drug analysis by capillary electrophoresis”. The 8th Annual
AstraZeneca Corporate Electrodriven Separations Sympo-
sium, 17-18 October 2001, Lund, Sweden (Invited plenary
lecturer).
Hansen SH. “The use of microemulsion electrokinetic chro-
matography (MEEKC) and dynamically coated capillaries for
drug analysis by capillary electrophoresis”.CE-Forum, Novo
Nordisk A/S, 11 December 2001 (Invited lecturer).
MEMBERSHIPS OF EXTERNAL COUNCILS
AND BOARDS
Claus Selch Larsen is a member of the Danish Academy of
Technological Sciences, chairman of the Biopharmaceutical
Section, Danish Pharmaceutical Society, member of Fagligt
Forum under The Danish Council for Scientific and Industrial
DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY
PAGE 41
Research (until July 2001), member of the editorial board for
Europian Journal of Pharmaceutical Sciences, and member of
the scientific advisory board for the biotech company Zealand
Pharmaceuticals (until June 2001).
Bente Gammelgaard is a member of Centre for Educational
Development in University Science
Bent Halling-Sørensen is external censor at the Technical
University of Denmark.
Steen Honoré Hansen Chairman of The Chromatographic
Society, Scandinavian Section and President of The
Separation Sciences Foundation. Member of the board of
ProPharma A/S and the board of The Propolis Research
Center A/S. Member of the Chemical Working Party and the
Working Party for Natural Products of the Pharmacopoeial
Board in Denmark. Member of the Commission and of the
Expert Group no.10B under the European Pharmacopoeia
Commission, Strasbourg.
Svend Erik Jørgensen is editor in chief of Ecological Model-
ling and Member of ILEC’s scientific committee (International
Lake Environmental Committee). Since 1988 bureau member.
Since 1995 President (chairman). He also spends a lot of his
time as a member of the following editorial boards: Water
Resource Developments, General Systems, Urban Systems,
Environmental Software and Modelling, Ecological Engineer-
ing, Journal of Analytical and Environmental Chemistry, Lakes
and Reservoirs, Research and Management, SAR- and QSAR
in Environmental Research, Environmental Modelling, Ecologi-
cal Indicator (Associate editor in chief) and Ecohydrology.
Member of the board for “The Summer School in Venice”,
1988 - present. Honorary Chairman of ICEI (International
Committee of Environmental Indices). Member of Scientific
Advisory board for IMAR (Marine Research Institute), Coimbra
Portugal, 1998 – present. Referee for IFS (International
Foundation for Science) 1994 - present.
Member of an Expert Panel (5 members), focusing on
Application of Models to develop ERA for chemicals (U.S. -
EPA, 1999 - ). Member of a UNESCO board for
Ecohydrology, 2001- present.
PROJECTS
ANALYTICAL CHEMISTRY
Capillary electrophoresis (CE)
New principles of performing CE with high electroosmotic
flow at low pH have been achived using a number of dynamic
coatings of the internal surfaces of fused silica capillaries. The
principles have been applied in bioanalyses of small as well
as of larger molecules (proteins). Furthermore, this new sepa-
ration technique have been hyphenated to ICP-MS as well as
to sheathless MS which also will inprove the applicability with-
in bioanalyse and thus for use in studies of drug metabolism.
Microemulsions have also been explored for use in drug
analysis, purity testing of drug substances and in bioanalysis.
(Jette Tjørnelund, Jørgen Olsen, Anette Gemal Jensen, Stig
Pedersen-Bjergaard, University of Oslo, Inga Bjørnsdottir,
Dina Tawfik Mohammed El-Sherbiny, Charlotte Gabel Jensen
and Steen Honoré Hansen)
Drug metabolism
The metabolism of drugs are compared in various in vivo
models (liver slices, liver homogenates as well as isolated en-
zyme systems). For this purpose selected drug substances
(e.g. naproxen, tolfenamic acid, ibuprofen, warfarin and dex-
trometrophan) are used as probes. Analytical chemical meth-
ods such as HPLC, HPLC-MS and HPLC-NMR have been
used to study the formation of metabolites in the models test-
ed. The reactivity of phase II metabolites towards proteins
have been an important issue.
A major field is reactive drug metabolites and their possible
role in ideosyncratic drug reactions. Focus has been on acyl-
glucuronides and acyl-CoA-adducts. The formation of CoA-
adducts results in the incorporation of the drug substances
into a number of endogenous metabolic pathways.
(Inga Bjørnsdottir, Claus Cornett, Steen Honoré Hansen,
Rasmus Worm Mortensen, Jørgen Olsen, Nina Hagen, Jette
Tjørnelund, Christian Skonberg, Ulrik Sidenius, Jane K.
Johannessen, prof. Ian T. Wilson, AstraZeneca, UK and prof.
Jeremy K. Nicholson, University of London, UK)
Hyphenation techniques
In order to obtain more data information faster different kinds
of couplings between separation techniques with spectro-
scopic techniques have been studied. Of special interest are
the following couplings: LC-NMR-MS/MS; CE-NMR; CE-
MS/MS; CE-ICP-MS. The LC-MNR-MS/MS hyphenation have
been used for the investigation of constituents and Hypericum
perforatum and other plants. A system for ion pair HPLC-
NMR-MS have also been developed for identification of impu-
rities in basic drug substances.
(Steen Honoré Hansen, Jette Tjørnelund, Claus Cornett,
Anette Gemal Jensen, Jørgen Olsen, Inga Bjørnsdottir, prof.
Ian D. Wilson, AstraZeneca, UK)
Quality control of drug substances
A project that involves development and validation of analyti-
cal chemical methods for determination of identity and purity.
The project is performed in collaboration with members of a
group of experts under the European Pharmacopoeia Commission.
(Alex Mehlsen Sørensen, Steen Honoré Hansen)
ANNUAL REPORT 2000–2001
PAGE 42
Mononuclear metalloproteins
Intramolecular electron transfer
Intramolecular electron transfer (ET) in bacterial proteins like
the azurins has provided basis for experimental as well as
theoretical studies of biological electron transport. With a
copper ion attached directly to amino acids and without the
presence of foreign group like e.g. heme we have the sim-
plest possible prosthetic group, namely the copper ion itself.
The protein is characteristic with its very robust �-sheet con-
struction and since the three dimensional structure has been
determined for a large group of azurins from different bacterial
origin as well as for many mutated proteins it is an ideal can-
didate for studies of relationships between structure and re-
activity. Systematic exchange of amino acids have provided
important information in this respect, and we now pursue
studies on intramolecular ET in azurin mutants with very large
driving force. We have so far been able to determine the reor-
ganization free energy for a �-sheet protein and determined
the electronic tunneling factor.
Kinetic isotope effects have so far never been treated, nei-
ther theoretically nor experimentally, for the biologically impor-
tant non-adiabatic ET processes. Not only the dynamic pro-
perties for H2O and D2O are significantly different, but also
the local structures of the two solvents vary. These parame-
ters influence the polarization correlation distance and lead to
changes in solvatisation and cause a definite deuterium iso-
tope effect. We have recently published our studies on ther-
modynamic and kinetic isotope effects on azurin.
Another interesting aspect of biological ET is the effect of
polarization on the long distance electronic coupling. Profes-
sor Robert Huber’s group at the Max Planck Instute in
Martinsried has produced a new type of “atomic” mutants
where certain hydrogen atoms in aromatic amino acid
residues have been exchanged by fluorine atoms. This substi-
tution is practically isosteric (the x-ray structures of the pro-
teins have been determined) while the polarity of the fluorinat-
ed side chains has been inverted. We are presently studying
the electronic couplings in these mutants by determining the
rates of ET.
Purple azurin
Structure and spectroscopy
The effect of axial ligand mutation on the binuclear CuA site in
a recombinant azurin bas has been investigated by advanced
magneto-spectroscopic techniques. The changes in the spin
density in the CuA site, as manifested by the hyperfine cou-
plings of the weakly and strongly coupled nitrogens, and of
the cysteine protons, were followed using a combination of
advanced EPR techniques. X-band (9 GHz) electron-spin-
echo envelope modulation (ESEEM) and two-dimensional (2D)
hyperfine sublevel correlation (HYSCORE) spectroscopy were
employed to measure the weakly coupled N-14 nuclei, and X-
and W-band (95 GHz) pulsed electron-nuclear double reso-
nance (ENDOR) spectroscopy for probing the strongly cou-
pled N-14 nuclei and the protons. The high field measure-
ments were extremely useful as they allowed us to resolve the
T2 and CuA signals in the g❑ region and gave H-1 ENDOR
spectra free of overlapping N-14 signals. These effects were
associated with an increase in the Cu-Cu distance and subtle
changes in the geometry of the Cu2-S2 core which are con-
sistent with the electronic structural model we have devel-
oped earlier.
DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY
PAGE 43
Multicentered metalloproteins and -enzymes
During the last years we have studied intramolecular ET in
multi centered macromolecules. An important issue which we
want to pursue is the coupling between electron transport
and coordination of the oxidizing substrate (e.g. O2 and NO2).
Gating processes where rearrangements of nuclei often be-
comes rate determining has so far not been studied in suffi-
cient detail, although we have already encountered examples
of intramolecular ET which is controlled by O2-coordination.
CuNiR
Denitrification is one of the most important and concomitantly
one of the most complicated biological ET processes. In col-
laboration with a British group we study the kinetics of enzy-
matic nitrite reduction by the copper containing nitrite reduc-
tase from Alcaligenes bacteria in an attempt to throw light on
the connection between structure, substrate binding, and re-
activity. CuNiR catalyzes the one-electron reduction of nitrite
to NO. We have already publishes results on the native en-
zyme and are presently studying different single site mutated
enzymes.
CD1NiR
The heme containing nitrite reductase from Pseudomonas
bacteria is another respiratory enzyme that we presently
study. Like the above copper enzyme it catalyzes the one-
electron reduction of nitrite to NO as well as the four-electron
reduction of dioxygen to water. Cytochrome cd1 nitrite reduc-
tase is a homodimer, each monomer containing one c-type
and one d1-type heme as prosthetic groups. The interheme
distances across the dimer interface of at least 3.8 nm ensure
electron transfer between monomers to be negligible, howev-
er. CD1NiR constitutes an optimal system for studies of the
connection between intramolecular heme ET and intermolec-
ular ET between substrates and enzyme. There has been
considerable debate about the relevance of structural chan-
ges including ligand switching during redox cycling and the
physiological implications of a possible gating mechanism.
We have already established a cooperativity between the
hemes and a dependence of ET rates on the reduction state
of the enzyme. The first part of our studies is now in print.
(Ole Farver in collaboration with: G.W. Canters, Inst. of
Chemistry, Leiden Universitet; R.R.Eady, Nitrogen Fixation
Lab., Norwich; O. Éinarsdóttir, Dept. of Chemistry and
Biochemistry, UCSC; D. Goldfarb, Dept. of Chemical Physics,
Weizmann Institute; R. Huber, Max Planck Inst. für Biochemie,
Martinsried; P.M.H. Kroneck, Dept. of Biology, Konstanz
Universitet; Y. Lu, Dept. of Chemistry, University of Illinois;
I.Pecht, Dept. of Immunology, Weizmann Institute; Lars K.
Skov, Kemisk Institut, KU; Jens Ulstrup, Kemisk Institut, DTU)
Selenium metabolism in humans
- speciation in biological samples
Selenium is an essential element that exerts its effects via the
selenoproteins and so far more than 30 selenoproteins have
been identified. The biological functions of all these proteins
have not been completely elucidated yet, but some of the
well characterized proteins are involved in antioxidative pro-
cesses in the body. In recent years the element has attract-
ed some attention as a possible protective agent against
certain forms of cancer. The cancer protective effect was
observed after prolonged intake of doses exceeding the
amounts necessary to keep the essential selenoproteins fully
functional. Thus, the the protective effect may be due to
other selenium compounds than the selenoproteins.
However, the metabolism of selenium is far from com-
pletely understood and the majority of earlier studies on se-
lenium metabolism were performed in vitro or in animal ex-
periments.
The main purpose of this project is to separate, identify
and quantify the different selenium containing compunds in
human biological samples - mainly plasma and urin - with
the ultimate aim of improving the understanding of human
selenium metabolism.
This involves the use of hyphenated techniques where dif-
ferent separation systems are coupled to the ICP-MS (Induc-
tively Coupled Plasma Mass Spectrometry) or MS detectors.
The separation techniques comprise chromatographic tech-
niques as reversed phase, ion-exchange and ion-pairing
chromatography together with capillary electrophoresis.
Special interest is taken in development of interfaces be-
tween the separation systems and the ICP-MS detector in or-
der to solve problems with incompatibility between optimum
flow ranges. Furthermore, solutions for circumventing prob-
lems based on the different compatibility of the preferred sol-
PAGE 44
ANNUAL REPORT 2000–2001
vents between the separation system and the detector are
examined.
As the natural concentrations of the selenium species is at
the low µg/L level and some of the compounds are suspect-
ed to be unstable, different pretreatment procedures are in-
vestigated and stability studies are undertaken.
(Bente Gammelgaard, Ole Jøns, Lars Bendahl, Ole Farver)
Trace multielement analysis in biological material
This project involves the simultaneous analysis of trace ele-
ments with influence on human health with focus on interac-
tion between the elements. The analytical technique is ICP-
MS.
(Bente Gammelgaard, Ole Jøns)
Environmental risk assessment of pharmaceuticals
Antibiotics are used widely across Europe to treat farm ani-
mals.
Once released to the environment, the pharmaceuticals and
their metabolites may persist and have the potential to runoff
to surface waters or leach to groundwaters where they can
impact human and environmental health. Unlike other classes
of substances (e.g. pesticide, metals and nutrients), the envi-
ronmental fate of veterinary pharmaceuticals is poorly under-
stood. A 3 year project is therefore being performed involving
modelling, laboratory, semi-field and field studies. The aim of
the study is to identify those factors and processes affecting
the fate of veterinary pharmaceuticals in order to adapt exist-
ing risk assessment models or to develop new models.
Laboratory studies will investigate sorption, degradability and
ecotoxicity of a range of veterinary pharmaceuticals. To do so
a range of new analytical methods especially on LC-MS-MS
has to be developed.
The results of these studies will be used to assess currently
available models and, where appropriate, the models will be
adapted to cope with pharmaceuticals. A range of scenarios
will be developed to assess the risk of veterinary pharmaceu-
ticals.
(Flemming Ingerslev, Anne Marie Jacobsen, Ann-Louise
Steinicke-Larsen, Anne Lykkeberg, Jette Tjørnelund and Bent
Halling-Sørensen together with several international research
groups)
Hormonally active agents in the environment
Over the past ten years it has appeared that a number envi-
ronmental contaminants are able to provoke adverse changes
in endocrine systems in humans and in the environment. The
research within this area has primarily been focusing on the
development of a test aimed at screening the endocrine ef-
fects of chemicals on the crustacean, Acartia Tonsa. Currently
an assay for testing endocrine effects using on breast-cancer
cells, the E-screen method, is under development.
The analytical chemical aspects
has been put more in focus in a
recently started project. In this
project, methods for precontration
of surface water is developed, an-
alytical methods (HPLC-MS-MS)
and the previous mentioned bioas-
says is used in the search of an
overall picture of the estrogen po-
tential of surface waters.
(Henrik Rasmus Andersen, Søren
Nors Nielsen, Flemming Ingerslev
and Bent Halling-Sørensen togeth-
er with the Technical University of
Denmark)
Parabens, a group of com-
pounds possessing estrogenic
potency in in-vitro assays –
what is the toxicological and
ecotoxicological significance of
these findings?
In the beginning of the 1990´s it was discovered that a variety
of chemical compounds used in various activities such as
agriculture (pesticides), industry (chemicals), food and phar-
maceuticals (preservatives), as well as natural compounds
derived from plants and fungi, posses estrogenic or other
hormonal effects detectable in various in-vitro and in-vivo as-
says. These effects occurred despite their low structural simi-
larity to the natural hormones. The toxicological and ecotoxi-
cological significances of these findings are not always clear.
Such finding often seems to provoke a heavy debate in the
public media and creates an immediate public demand of
banning the chemical in question. Last summer Denmark
faced such a discussion when the public media disclosed
that UV-screens used in e.g. sun lotion to reduce UV-radiation
to the skin, possessed estrogen potency in both an in-vitro
assay and for some of them also in an in-vivo assay. The
newspapers and green organisations claimed an immediate
ban of all sun lotions that contained these UV-screens. As a
result, the population was left with the dilemma of choosing
between two risks. Evolution of sun burns with potential risk
to later develop skin cancer or being exposed to hormonally
active chemicals.
To limit the number of such often hasty conclusions regard-
ing the use of chemicals, risk assessment methodologies
should be much more developed in the direction of a com-
municative management tool in today’s society. The strength
of risk assessment as a management tool is that it provides a
means for handling the “unknowns”. The “unknowns” that in
fact exist for most chemicals are handled by using precau-
tionary principles in such assessment. Furthermore, risk as-
DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY
PAGE 45
Mille developing the MCF7 assay
sessment also helps us to identify where we need to enhance
our knowledge and perform more experiments.
The parabens is also an example of recently found “xeno-
estrogens”. In the sections of environmental chemistry and
toxicology at the Royal Danish School of Pharmacy we have
lately studied the parabens. Current literature shows that the
estrogenic potency of the parabens increases markedly with
the size of the molecule as well as with the branching of the
alkyl-substitutents. Figure 1 shows the general structure of
parabens together with the natural estrogen hormone, 17�-
estradiol, and 4-alkylphenols which have been proved as
xeno-estrogens. The figure shows that the parabens does not
resemble 17�-estradiol at all, but that there is some similarity
with alkylphenols. (Alkylphenols were identified as xenoestro-
gens a decade ago based on effects in both rats and fish and
their use is now regulated) Parabens are known to be unsta-
ble in different matrices due to their vulnerability towards ester
hydrolysis.
Parabens are often used in the western world as preserva-
tives for food, cosmetics, pharmaceuticals (used in e.g. solu-
tions for injection or infusion) and health care products. The
compounds are nearly always used as mixtures of several n-
alkyl parabens such as n-methyl-, n-ethyl, n-propyl, and n-
butylparabens, and their branched isomers to broaden the
spectrum of preservation. The compounds are regulated in
Denmark so that a maximum of 300-mg paraben/kg is al-
lowed for preserving food. Furthermore, cosmetics is permit-
ted to contain up to 0.4 % of a single paraben and no more
than 0.8 % of a paraben mixture. No legislation rules the use
of parabens in pharmaceuticals.
We tested the estrogenic activity of a number of
parabens, including both the n-forms and iso-
forms (e.g. both n-butylparaben and iso-
butylparaben) with the so-called E-
Screen assay. In this assay,
a breast cancer cell line (the MCF-7 cells) proliferates due to
the presence of estrogenic active chemicals. In total twelve
parabens were assessed.
Results showed as expected that the proliferation of MCF7
cells increased with the dose of all twelve parabens. The rela-
tive potencies of e.g. 2-ethylhexylparabens and ethylparaben
are 5,500 times and 230,000 lower, respectively, compared to
17�-estradiol. We also found that the iso-parabens were sig-
nificantly more estrogenic than the n-parabens.
The question was now whether these findings could imply
that parabens would be a risk for humans or the environment.
The answer is at present: It is not likely. However, results from
in-vitro testing can of course not standalone. Proper risk as-
sessment should be performed, including other relevant infor-
mations such as physico-chemical data of the chemicals, an-
alytical measurement of paraben mixtures, covering a number
of relevant exposure scenarios to both humans and the envi-
ronment.
To assess the parabens we therefore investigated two rele-
vant scenarios that especially were identified as vulnerable to
humans and to the environment with regard to the identified
exposure routes. In the following we give a very brief sum-
mery of the scenarios and of the calculations included.
In scenario I, we attempt to assess the exposure of para-
bens in pharmaceuticals, dosed as daily injections (Heparin
preserved with methylparaben) to a pregnant woman from the
2th to 35th week of pregnancy. This is the most vulnerable peri-
od of the pregnancy for the foetus to be exposed to the com-
pounds. Other pharmaceuticals containing parabens were also
assessed. It was concluded that the highest calculated risk of
introducing cell deformities in the foetus induced by parabens
was one out of a million, compared to similar data for DES
(synthetic estrogen). This is generally considered as an ac-
ceptable risk. But still, a few questions are left. Some lotions
include the iso-parabens identified as more potent ones. A
similar assessment would need non-existing data for the iso-
parabens or could we for instance use in vivo experiments on
linear parabens to predict the risk of using the branched para-
bens? Furthermore, we do not know if the ester hydrolysis in
e.g. the blood or sewage breaks down the branched com-
pounds as rapid as the linear ones.
In scenario II, similarily, we tried to assess the risk for the
aquatic environment using a scenario covering the sewage
treatment plant. Parabens used in health care products or
cosmetics are transported with sewage water from the shower
or bathtub to the sewage treatment plant. In the environment
parameters such as biodegradation, sorption, hydrolysis, pH
and photolysis may have impact on the resulting concentration
of the compounds in the treated effluent. The calculated or
measured concentration is then compared to effect concen-
trations on relevant species (acute or chronic effects) from dif-
ferent trophic levels of the aquatic food chain. If the calculated
ANNUAL REPORT 2000–2001
PAGE 46
or measured concentrations in the treated sewage exceed the
effect concentrations times an assessment factor, the com-
pounds may be a risk for the environment. Different scenarios
taking in to account more or less information on the fate of the
parabens, all gave results indicating that the concentrations of
the compounds in the sewage were at least a factor 100 –
1000 below the effect concentrations. But our study also re-
vealed that available data on relevant chronic effect concentra-
tions are very sparse so that more relevant data should be
gathered. In other words a definitive conclusion regarding the
risk of parabens in scenario II can not be given.
Our research study aim to pass a few messages. The pub-
lic media is often ready to conclude that society is facing a
risk connected with chemicals based on too few facts.
1. The chemicals (parabens), even though they exhibit estro-
gen potency in a in-vitro assay, does not impose a risk
using the available informations in relevant scenarios.
2. Furthermore, the same chemicals may (in this case the
parabens), because of a variety of applications, be the
subject of quite different exposure scenarios.
3. The biological and chemical fate of the chemicals are im-
portant informations to include in a risk assessment and
might be quit different for the same compound in different
environments.
A much broader awareness of risk assessment as a man-
agement tool able to communicate risks to society is there-
fore urgently wanted. We should learn to communicate our
conclusions not only based on documented informations but
also on the “unknowns” by using precautionary principles in
the assessment. This would balance the communication to
society of the risk of chemicals.
As a further conclusion we might ad that the present study
needed information from several other disciplines than toxi-
cology in order to fulfil the assessments. Analytical chemistry
could be used both to identify the included parabens in the
formulations and analyse the treated sewage. Furthermore we
needed physical chemistry to assess the stability of the
parabens in different matrices such as blood and sewage.
Knowledge about microbiology and biology were used to
assess the biodegradation and perform the MCF7 assay.
Furthermore good skills in literature survey is important in risk
assessment.
(Henrik R. Andersen, Morten M. Pedersen, Mille Holst-
Jørgensen, Søren Nors Nielsen, Flemming Ingerslev, Erling
Sonnich Thomsen and Bent Halling-Sørensen)
CHEMICAL TOXICOLOGY
For decades this department has served as a center of
knowledge on hazardous chemicals, both on handling and in
case of accidents. The number of calls is about 50 per year.
Several of these inquiries have resulted in further toxicological
evaluations. Two main research branches have appeared: in-
halation toxicology (pulmonary edema, toxic smoke from fires,
criteria for evacuation, etc.) and clinical toxicology (hospital
reception and treatment of patients suffering from the effects
of chemical accidents, antidote preparedness, etc.).
A compulsory course on toxicology is given. An important
aspect is that the students are supposed to have a good
knowledge of chemical compounds and of the properties of
groups of chemicals. The reason is that many of the prob-
lems from worker’s and consumer’s safety, from environmen-
tal pollution and from chemical disasters implies knowledge of
chemistry and toxicology, simultaneously. Similar considera-
tions apply to the safety course at the beginning of the study.
Projects on toxicology and chemical safety:
• Releases of toxic gases from chemical spills or from chem-
ical fires.
• Antidotes and procedures for acute poisonings, especially
if these can be used by laypersons.
• The combination of chemistry and toxicology with technical
and tactical knowledge forms the basis for advising e.g.
the authorities, the politicians, and the media on hazardous
chemicals: the risks and the preventive and mitigative
measures. Unfortunately, this activity becomes increasingly
relevant as the knowledge of chemistry and toxicology de-
creases both for the groups mentioned and in the general
public.
(Erling Sonnich Thomsen)
PHARMACEUTICAL CHEMISTRY
Prolonged release of bupivacaine after subcutaneous in-
jection of an oil mixture formulation in the rat
For decades anaesthesiologists have sought an agent that
would provide local anaesthesia lasting for days rather than
hours. Such an agent would be invaluable for providing post-
operative pain control and for treatment of chronic pain.
Among other characteristics the ideal long acting local anaes-
thetic agent should affect sensory, but not motor fibers. No
agent currently exists that possesses all the desired proper-
ties. Therefore, most efforts have primarily been concerned
with modifying formulations of existing local anaesthetics to
yield new mechanisms that will sustain ultra long duration
anaesthesia.
Bupivacaine is a frequently used local anaesthetic. The
treatment of wound sites with administration of bupivacaine
at or near the end of surgery is common practise. For clinical
use the drug is formulated as an aqueous solution (Marcain®)
and the duration of action is approximately 4-6 hours. The
site of action of bupivacaine is the tissue surrounding the in-
jection area, however, a significant amount of the dose enters
into the blood shortly after the injection. When bupivacaine is
DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY
PAGE 47
injected as an aqueous solution it is readily mixed with the tis-
sue fluid and distributed to both the nerve cells and the
blood. High concentrations of bupivacaine in the blood might
give rise to severe cardiac toxicity and therefore have to be
avoided.
A means to obtain prolonged bupivacaine release and at
the same time to minimise toxic side effects, is to incorporate
the drug substance into a formulation from which it is slowly
released. Bupivacaine can be dissolved in vegetable oil mix-
tures (in the free base form). These oils are not miscible with
water and after injection of such bupivacaine oil solutions the
drug has to be released into the aqueous tissue fluid before it
can exert its action. By variation of the composition of the oil
mixture it is possible to vary the bupivacaine release rate from
the oil. As a part of a PhD project bupivacaine was injected
subcutaneously in rats in an aqueous and in an oil
mixture. First, the rats were given Marcain® and one
week later the oil formulation containing the same amount of
bupivacaine was injected. After each injection blood samples
were taken as a function of time and the concentration of
bupivacaine in each sample was determined. As seen from
Figure 2 relatively high plasma concentrations of bupivacaine
is initially obtained after injection of Marcain®, and the con-
centration in the blood declines rather fast with time. In con-
trast, injection of the oil solution gives rise to a relatively con-
stant plasma concentration of bupivacaine over an extended
period of time (up to 24 hours). In addition, compared to
Marcain® the oil solution initially results in much lower blood
concentrations thus minimising the risk of unwanted bupiva-
caine side effects. The study indicates that it might be possi-
ble to design pharmaceutical formulations endowed extended
duration of action.
(Claus Selch Larsen)
1. PARENTERAL DEPOTS:
1a. Pharmaceutical chemical
characterisation of oil solutions
The aim of the project has been to develop and characterise
an in vitro release model to be used in investigations of the
rate of release of drug substances/prodrugs from oil solutions
including a chemical kinetic description of the release pro-
cesses. The model has been used to study the influence of
various formulation factors on the control of the rate of drug
release from oil formulations. Furthermore the model has
been used to establish an in vitro-in vivo correlation.
(Dorrit Bjerg Larsen (PhD student), Karin Fredholt (H.
Lundbeck A/S) and Claus Selch Larsen)
1b. Design of prodrugs of polar drug substances aiming
at obtaining depot effect after parenteral administration
Polar drug/model drug substances under investigation include
nicotinic acid, local anaesthetics and dipeptides. The focus of
the project embraces: (i) development of an in vitro release
model for the assessment of the rate of release of lipophilic
prodrug derivatives from oil solutions, (ii) comparison of (a) po-
tential lipase mediated degradation of clinically used oil vehi-
cles, and (b) the rate of disapperance of such oil vehicles from
the injection site after i.m. and s.c. injection in pigs, and (iii)
enhance oil solubility of polar drug candidates by using the
prodrug approach in combination with hydrophobic ionpairing.
(Susan Weng Larsen (PhD student), Gitte Juel Friis (Coloplast
A/S), Michael Ankersen (Novo Nordisk), and Claus Selch
Larsen)
1c. Design of low solubility salts of drug substances
The project aims at achieving greater insight into the effect of
structural parameters on the solubility of salts and the estab-
lishment of models for the prediction of aqueous solubility of
PAGE 48
A group of rats were given the same amount of bupivacaine by subcutaneous injection first as an
aqueous solution and second as an oil solution.
Plasma (blood) concentrations of bupivacaine determined after different time periods after subcuta-
neous injection in rats of the aqueous Marcain® solution (circles) and the oil solution (triangles).
ANNUAL REPORT 2000–2001P
lasm
a co
ncen
trat
ion
(ng/
ml)
Time (hours)
salts. A particular focus area is the formation of low solubility
salts of drug substances containing a carboxy or amino
group. The project includes preparation and pharmaceutical
chemical characterisation of salts, and in addition, aspects of
the design of in situ crystal suspension formulations.
(Henrik Parshad (PhD student), Karla Frydenvang and Tommy
Liljefors (Dept. Medicinal Chemistry), and Claus Selch Larsen)
2. PRODRUGS – IDENTIFICATION OF TRANSPORT
GROUPS EXHIBITING A BIOLOGICAL FUNCTIONALITY:
2a. Optimisation of oral bioavailability of drugs by avoid-
ance of first-pass metabolism
Many potential drug candidates are highly metabolised after
oral administration due to first-pass metabolism in the liver. It
is known that binding of drugs to tissue and plasma proteins
are important parameters influencing the metabolism and
elimination of such compounds. By using the prodrug ap-
proach the aim of this project is to investigate the feasibility of
incorporation of a biological functionality in the transport
group in order to circumvent or minimise liver first-pass
metabolism. As a start efforts will be devoted to identify
chemical structures (fatty acid-like structures) as transport
groups possessing optimal affinity to human serum albumin.
(Jesper Østergaard (PhD student), Helle Brøndsted, Lars
Dalgaard (H. Lundbeck A/S), and Claus Selch Larsen)
3. FACILITATION OF BIOMEMBRANE DRUG
TRANSPORT BY PRODRUG DESIGN:
3a. Prodrugs of nucleotide bases
Oligonucleotide-based therapy might be considered as a new
and highly specific tool for the treatment of diseases such as
cancer and virus infections. The therapeutic use of antisense
oligonucleotides is, however, hampered due to instability of
the backbone. In addition, the polar character of the
molecules is an impediment for their passage of biological
membranes. The aim of the project is (i) to optimise passive
transport of such agents over the bacterial cell wall by pro-
drug derivatisation, and (ii) to investigate the influence of the
physicochemical properties of such derivatives on the rate of
release from pharmaceutical matrices.
(Karsten Petersson (PhD student), Helle Brøndsted, Karen
Krogsfelt (Statens Serum Institut), and Claus Selch Larsen)
3b. Prodrug types of isoxazole structures
An interesting class of GABAA antagonists share an isoxazolol
ring. The polar nature of this ring structure at physiological pH
is less optimal as regards transport over biological mem-
branes. Such pharmacologically active agents may therefore
not be effectively delivered to their site of action: the central
nervous system. The aim of the project is to identify suitable
prodrug types for the isoxazolol structure which combine im-
proved transport properties with desirable cleavage rates.
(Bente Frølund (Dept. Medicinal Chemistry) and Claus Selch
Larsen)
4. MANIPULATION OF DRUG SOLUBILITY:
4a. Use of the combination of prodrug design
and salt formation - a strategy to enhance
aqueous solubility of drugs
By modern medicinal chemistry a great number of com-
pounds exhibiting desired receptor profiles emerge. Unfor-
tunately, insufficient water solubility resulting in low and vari-
able bioavailability after oral administration prevents many
pharmacologically interesting chemical entities from further
development. Improvement of this basic physicochemical
property might be achieved by employing the prodrug ap-
proach which involves only a transient masking of the physic-
ochemical properties since the parent active agent is regener-
ated in vivo. Furthermore, it is well known that the use of dif-
ferent counterions can result in salts differing several orders of
magnitude with respect to aqueous solubility. Thus, the aim of
the project is to enhance the aqueous solubility of poorly wa-
ter-soluble compounds achieved by the combined approach
involving prodrug design and optimisation of salt formation.
(Anders Bach Nielsen (PhD student), Anders Buur (H.
Lundbeck A/S), Karla Frydenvang and Tommy Liljefors (Dept.
Medicinal Chemistry) and Claus Selch Larsen).
DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY
PAGE 49
Department of Medicinal Chemistry
PAGE 50
Head of Department: Ulf Madsen, Associate Professor, PhD teaching gives students in-depth knowledge of organic chem-
istry, and integrates chemistry and biology into the process of
educating drug experts.
RESEARCH
The research profile of the Department is illustrated by the fig-
ure below and the general description of the research groups.
More detailed descriptions of selected projects are given un-
der Projects.
The Department of Medicinal Chemistry conducts teaching
and research in organic chemistry, spectroscopy, medicinal
chemistry, natural products chemistry, pharmacognosy and
structural chemistry. All subjects are related to drug research
and because virtually all drugs used in therapy today are or-
ganic compounds, detailed knowledge of organic chemistry
and chemical structure is indispensable for drug experts. The
Research areas at the Department.
ANNUAL REPORT 2000–2001
PHARMACOGNOSY
The Pharmacognosy Group works with medicinal plants in
teaching and research. The research projects comprise a
range of disciplines from ethnobotany and chemotaxonomy
to bioassay guided fractionation of plant extracts and purifi-
cation of active compounds. Plant material is obtained from
the Tropics, mainly African countries (Burkina Faso, Kenya,
Nigeria, and Zimbabwe), the Mascarene Islands (Reunion and
Mauritius), as well as India and other Asian countries (Vietnam).
Plants used in traditional medicine are studied in selected bi-
ological assays for antimicrobial, antihypertensive, anthelmin-
tic and antimalarial activity. Most of these projects are carried
out as joint venture projects with scientists from tropical
countries and with colleagues from the Royal Danish School
of Pharmacy and other Danish research laboratories.
NATURAL PRODUCTS
In search of new leads with novel pharmacological properties,
it is of interest to test large numbers of compounds.
Therefore, the use of combinatorial libraries is of particular im-
portance to drug discovery. Nature provides an unsurpassed
source of chemical diversity, and combinatorial libraries of
natural products are an important supplement to synthetic
combinatorial libraries. Studies of natural products and of
their potential as drugs are the basic activity of the group.
Research includes plant selection, pharmacological charac-
terisation of the extracts, dereplication, structure elucidation
(mainly by NMR methods), phar-
macological characterisation of
pure constituents, and medicinal
chemistry in relation to promising
structures.
STRUCTURAL CHEMISTRY
The three-dimensional structures
of molecules provide important in-
formation about the properties of
the molecules, and thereby a key
to understanding the relationships
between molecular structure and
biological activity. The Structural
Chemistry Group uses experimen-
tal methods like X-ray crystallo-
graphy to determine the three-
dimensional structure of low-
molecular weight compounds,
macromolecules, e.g. receptors
and enzymes, and protein-ligand
complexes. Computational methods
like molecular mechanics and quantum mechanics are used
to predict molecular properties and to calculate molecular in-
teractions between the ligands (neurotransmitters, hormones,
enzyme inhibitors etc.) and their macromolecular target mole-
cules (receptors, enzymes etc.). By studying molecular inter-
actions, it is possible to construct so-called 3D-QSAR’s
(three-dimensional quantitative structure-activity relationships),
which enable new ligands to be designed and their biological
activity and selectivity predicted.
NEUROMEDICINAL CHEMISTRY
The goal of the Neuromedicinal Chemistry (NeMe) Group is to
design tools and model drugs, which interact specifically with
the target receptors. Bioisosteric principles (molecular mimi-
cry) are used extensively to transform endogenous transmitter
substances or naturally occurring compounds into receptor
specific model drugs. Structure-based design of new ligands
is performed in collaboration with the Structural Chemistry
Group. This is an integral part of the projects aiming at recep-
tors where sufficient data on the receptor proteins are avail-
able. An important aspect of all of these projects is to design
and synthesise the target molecules with established stereo-
chemistry. The enantiomers of pharmacologically active com-
pounds are frequently obtained by optical resolution methods
based on diastereomeric procedures or chiral chromato-
graphic (HPLC) separation techniques. Normally, the absolute
stereochemistry of enantiomers is established by X-ray crys-
tallographic methods supported by circular dichroism and
DEPARTMENT OF MEDICINAL CHEMISTRY
PAGE 51
HPLC parameters. Molecular pharmacology has become an
integral component of modern medicinal chemistry, and the
research activities of this part of the NeMe Group involve re-
ceptor cloning and pharmacological studies using mutated
and chimerised receptors. The NeMe Group has extensive
collaborative projects with the drug industry.
SYNTHETIC CHEMISTRY
The Synthesis Group is involved in the development of a
broad range of new synthetic methods and advanced tech-
niques including metalation reactions, transition metal cata-
lysed reactions, cyclisations and stereoselective processes.
The target molecules are diverse but frequently compounds
of biological relevance. The metalation reactions deal with the
preparation of mainly lithium, magnesium, zinc, boron, silicon
and tin compounds. Transition metal chemistry is focused on
palladium catalysed cross-couplings establishing C-C, C-N
and C-O bonds and is used, for example, in arylation and
heteroarylation reactions. Anionic cyclisation is another impor-
tant subject. Special attention is paid to monoselective, re-
gioselective and stereoselective protocols. Selectivity is
achieved by the use of designed directing, activated, or su-
peractivated groups in combination with suitable protecting
groups. Target compounds range from functionalised 5-mem-
bered nitrogen heterocycles, unnatural amino acids, peptides,
neurotransmitter analogs, bioisosters, prodrugs, transporter
conjugates and lipids to chiral ligands and acylation catalysts
for peptide synthesis. The studies include computational
methods with the aim of predicting reactivity, elucidating re-
action mechanisms and creating rules for rational design of
reaction sequences. Computations are also used to optimise
structural design. NMR-spectroscopy is used extensively for
structure elucidation and to establish correlations between
NMR parameters and physical and chemical properties.
TEACHING
The Department offers the following compulsory courses:
Organic Chemistry • Bioorganic Chemistry • Pharmacognosy
• Drug Design and Development. The courses in Organic
Chemistry and Pharmacognosy include laboratory training in
addition to lectures and class teaching.
The following elective courses are offered:
Spectroscopy • Medicinal Chemistry • Structural Chemistry •
Advanced Organic Chemistry • Phytochemistry, Pharmaca
and Toxins • Etnopharmacology • Herbal Medicines •
Intellectual Property Rights in Pharmaceutical Sciences.
Approximately 30 PhD students are enrolled at the
Department, three-quarters of them financed by external
funding.
The following PhD courses (taught in English) are offered:
Advanced Techniques in Synthetic Organic Chemistry •
Advanced Structural Chemistry and Molecular Modelling •
Receptor Structure and Function • Drug Design and
Discovery • In Vivo Neuropharmacolgy.
SCIENTIFIC GUESTS
Prof. Marco de Amici, Universita di Milano, Italy.
Dr Karine Audouze-Taboureau, NeuroSearch A/S, Ballerup,
Denmark.
Sir, Prof. Tom L. Blundell, University of Cambridge, United
Kingdom.
Prof. Lars Bohlin, University of Uppsala, Sweden.
Prof. Guiseppe Campiani, Universita’ degli Studi di Siena,
Italy.
Dr Paolo Conti, Universita di Milano, Italy.
Dr Caterina Fattorusso, Universita’ degli Studi di Siena, Italy.
Dr Michael H. Howard, DuPont Company, USA.
Dr Henry Hägerstrand, Åbo Akademi University, Finland.
Dr Elisabeth Marseglia, Cavendish Laboratory, Cambridge,
United Kingdom.
Dr Roman Laskowski, Birkbeck College, University of
London, United Kingdom.
Dr Hellen A. Oketch-Rabah, University of Nairobi, Kenya.
Prof. Algirdis Sackus, Kaunas University of Technology,
Lithuania.
Dr D. Shankar, Foundation for Revitalization of Local Health
Traditions, Bangalore, India.
Dr Tracy Spalding, Acadia Pharmaceuticals, San Diego,
California, USA.
Prof. Ronald Stenkamp, University of Washington, Seattle,
USA.
Prof. Olov Sterner, University of Lund, Sweden.
Dr Owe Wiborg, Aarhus University Hospital, Aarhus,
Denmark.
Prof. Jean-Marie Wurtz, Institut de Genetique et de Biologie
Moleculaire et Cellulaire, France.
GUESTS RESEARCHERS
PhD student Luca Guandalini, August-December 2001.
Dr Sonata Krikstolaityté, Kaunas University of Technology,
Lithuania, September 2000-June 2001.
Dr Elin S. Olafsdottir, University of Iceland, June-August
2001.
Dr Michael G. Rowan, University of Bath, United Kingdom,
July-August 2001.
ANNUAL REPORT 2000–2001
PAGE 52
ARRANGEMENTS
“Nordic Pharmacognosy Meeting”, June 2001.
Mini-symposium “Receptor Structure and Function”, May
16, 2001.
DANSYNC, Danish Centre for Synchrotron Based
Research, Annual Meeting, May 23, 2001.
Minisymposium “Drug Design Copenhagen 2001”, October
16, 2001.
“Seminars in Natural Products and Pharmacognosy” are a
monthly event at the Department.
MEMBERSHIP OF EXTERNAL COUNCILS AND BOARDS
Anne Adsersen
• Member of the Subcommittee on Pharmacognosy under
the Danish Pharmacopoeia Commission.
Mikael Begtrup
• Member of the steering group for the Department of
Physics and Chemistry, The Teaching University of
Denmark.
• Member of the Evaluation Center’s board for assessment of
the universities teaching in physics, mathematics and
chemistry.
• Member of the steering group and the scientific committee
for the 32nd Chemistry Olympiad.
• Member of the scientific committee for the European
Colloquia on Heterocyclic Chemistry.
• Member of the editorial board for Chemical Communi-
cations.
• Scientific editor for ARKIVOC, an electronic journal for
organic chemistry.
Hans Bräuner-Osborne
• Member of the Management Committee of the European
Federation for Medicinal Chemistry.
• Member of the board for the Danish Society for
Pharmacology and Toxicology.
Søren Brøgger Christensen
• Chairman of ”Studiefonden” of the Danish Union of
Pharmacists.
• Member of a panel, which evaluated the Department of
Horticulture, the Danish Institute of Agricultural Sciences,
Årslev.
Karla Frydenvang
• Member of the Danish National Committee for
Crystallography.
Lene Gudiksen
• Head of the Subcommittee on Pharmacognosy.
• Member of the Danish Pharmacopoeia Commission.
• National Representative in ESCOP (European Cooperative
for Phytotherapy) scientific committee.
Jerzy W. Jaroszewski
• Chairman of the Danish Chemical Society, Section of
Organic Chemistry.
Birthe Jensen
• Rector until May 1, 2001.
• Member of the board of UNI.C.
• Member of the board of MVA (Medicon Valley Academy).
• Member of the board of the Symbion Foundation until May
1, 2001.
• Member of the board of European Association of Faculties
of Pharmacy (EAFP).
• Chairman of board of the ULLA network until December 31,
2001.
• Chairman of Evaluation Panel, Pharmacy Education of
Helsinki University, December 2001.
Jette Sandholm Kastrup
• Member of the board for DANSYNC, Danish Centre for
Synchrotron Based Research.
Povl Krogsgaard-Larsen
• Member of the Danish Academy of Sciences and Letters.
• Member of the Danish Academy of Technical Sciences.
• Member of the Danish Academy of Natural Sciences.
• Member of the board of directors of the Carlsberg
Foundation.
• Member of the board of Carlsberg A/S.
• Chairman of the board of the Carlsberg Laboratory.
• Vice-chairman of the board of the Alfred Benzon
Foundation.
• Member of the Danish Rector’s Conference.
• Member of the board of the Symbion Foundation.
• Member of the board of the Danish Research Training Council.
• European editor of Journal of Medicinal Chemistry.
• Member of the editorial boards of 7 medicinal chemistry
and pharmaceutical journals.
Tommy Liljefors
• Member of the Management Committee of COST
(European Co-operation in the Field of Scientific and
DEPARTMENT OF MEDICINAL CHEMISTRY
PAGE 53
Technical Research) Action D13: “New molecules towards
human health care”.
• Member of the editorial board for Journal of Molecular
Graphics and Modelling.
Per Mølgaard
• Co-ordinating secretary for The International Tundra
Experiment (ITEX).
• Danish contact for the ethnobotanical section of AETFAT
(Association for the Taxonomy Study of the Flora of Tropical
Africa).
Nina Rønsted
• Member of the Council for Health Studies and Education.
Ulla Wagner Smitt
• Treasurer of The International Society for Ethnopharmacology.
DONATIONS AND GRANTS
Mikael Begtrup
DKK 100,000 – Carlsberg Research Prize (Carlsberg
Forskerpris).
Co-financing of a 300 MHz NMR spectrometer from the
Danish Council for Natural Sciences.
Financing of 1 PhD student from Løvens Kemiske Fabrik.
Co-financing of 5 PhD students and 1 post doc from Novo
Nordisk A/S.
Co-financing of 5 PhD students from Lundbeck A/S.
Hans Bräuner-Osborne
DKK 300,000 from The Danish Medical Research Council
for the project ”Molecular pharmacology and mechanistic
studies of family C G-protein coupled receptors”.
For additional research centre grants see ”Research Centres
Grants”.
Søren Brøgger Christensen
DKK 500,000 a year from the Danish Cancer Society
(Kræftens Bekæmpelse) for the project ”Development of tis-
sue-specific prodrugs for treatment of prostatic cancer”
(1.1.02-31.12.04).
USD 70,000 from the National Cancer Institute, Maryland,
USA for development of methods for large-scale isolation and
prodrug preparation of Thapsigargin.
Danida ENRECA project ”The Accra-Copenhagen Research
Link: Malaria Research Programme” (1999-2003).
A grant together with Karen Krogfelt (Statens Seruminstitut)
from the Danish Medical Research Council for the project
”Anti-adhesion therapy” (1999-2002).
Rasmus Prætorius Clausen
DKK 1,140,000 from the Lundbeck Foundation in a 3-year
period.
Henrik Franzyk
DKK 2,997,000 from the Danish Technical Research
Council for the Talent-project “Solid-phase Synthesis of
Neuroactive Polyamine Derivatives”.
DKK 150,000 from the Carlsberg Foundation to support this
research.
Karla Frydenvang
DKK 495,000 from Alfred Benzon Foundation for the pro-
ject ”Solid state properties of pharmaceutically relevant com-
pounds” (31.8.01-30.8.02).
Jerzy W. Jaroszewski
DKK 3,500,000 from Apotekerfondet for purchase of NMR
equipment.
DKK 250,000 from the Danish Medical Council for the pro-
ject ”Analogues of polyamine wasp toxins”.
DKK 254,058 from the Novo Nordisk Foundation for the
project ”Selective antagonists at ionotropic receptors”.
DKK 25,000 from Ben-Gurion University, Israel, for studies
of Balanites.
Danida ENRECA project ”Ethnopharmacology of Indian
medicinal plants” (expired in June 2001)
Danida ENRECA project ”Medicinal plants from East Africa”.
For additional research centre grants see ”Research Centres
Grants”.
Christina Kasper
DKK 391,636 from the Carlsberg Foundation for the project
”Studies of glutamate receptors with speciel reference to
structure-based drug design” (1.1.01-31.12.01).
Jørgen Bonefeld Kristensen
DKK 62,712 from Novo Nordisk A/S - a one-year Novo
Nordisk Scholarship.
Ingrid Kjøller Larsen
DKK 70,000 from DANSYNC, Danish Centre for
Synchrotron Based Research.
DKK 250,000 from the Danish Medical Research Council
for the project ”Protein crystallography in drug research.
Structure determination of biomacromolecules and their com-
plexes with ligands/drugs (2001-2003)”.
DKK 80,000 from the Novo Nordisk Foundation for the pro-
ject ”Protein crystallography in drug research. Characterization
of biomacromolecules by dynamic light scattering”.
For additional research centre grants see ”Research Centres
Grants”.
ANNUAL REPORT 2000–2001
PAGE 54
Povl Krogsgaard-Larsen
DKK 1,836,000 from the ”Drug Design and Transport Centre”
granted by the Danish Medical Research Council (account-
ing year 2000-2001).
ECU 177,00 together with Jerzy W. Jaroszewski from EU.
DKK 400,000 from the Alfred Benzon Foundation.
For additional research centre grants see ”Research Centres
Grants”.
Per Mølgaard
DKK 150,000 from the Commission for Scientific Research
in Greenland for the project ”Development of analytical
methods for secondary compounds in Arctic plants”.
DKK 180,000 together with Søren Brøgger Christensen from
Danida via a grant to Ole Skovmand, Intelligent control for
supporting an environmental project in Burkina Faso, Africa.
DKK 210,000 from the Danish Research Council for the
project ”Special chemicals and pharmaceuticals from plants”.
Britt Petersson
PhD grant from DANSYNC, Danish Centre for Synchrotron
Based Research (2000-2003).
RESEARCH CENTRES GRANTS
Povl Krogsgaard-Larsen, Ingrid Kjøller Larsen and Tommy
Liljefors: DKK 6,000,000 from the Lundbeck Foundation for
the research programme ”Neuro-medicinal chemistry.
Molecular design, specificity and recognition” (1999-2001).
Povl Krogsgaard-Larsen, who is the co-ordinator of this pro-
gramme received DKK 1,150,000 per year. Ingrid Kjøller
Larsen and Tommy Liljefors each received DKK 425,000 per
year.
Hans Bräuner-Osborne , Jerzy W. Jaroszewski, Ingrid Kjøller
Larsen and Tommy Liljefors
DKK 6.700.000 from the research centre NeuroScience
PharmaBiotec A Strategic Drug Research Centre” (1997-
2001). The centre is granted by Danish Medical Research
Council with totally DKK 29,700,000. Povl Krogsgaard-
Larsen is director of the centre.
Ingrid Kjøller Larsen, Tommy Liljefors, Jerzy W. Jaroszewski
and Povl Krogsgaard-Larsen: DKK 635,000 from the
PharmaBiotec funding, which from January 2000 became a
part of the annual appropriation to the Royal Danish School
of Pharmacy (until January 2000 PharmaBiotec was funded
by the State Biotechnology Programme).
PROJECTS
Special chemicals and pharmaceuticals from plants
There is a great need for medicinal plant products of a high
quality, and Danish agriculture is interested in alternative crop
plants to the traditionally grown cash crops. Our research
work comprises plant chemicals like fatty acids, caffeic acid
derivatives, alkamides and iridoids for technical and medicinal
purposes. These compounds are all plant derived, and in
most cases there is only little information of how to grow
these plants, especially under Danish conditions. To deter-
mine the quality of medicinal plants validated analytical meth-
ods are highly important, and a major part of the project is
confined to the establishment of validated analytical methods.
In connection with plant production, diurnal and seasonal
variation in plant secondary compounds may play a central
role.
DEPARTMENT OF MEDICINAL CHEMISTRY
Echinacea purpurea, the purple coneflower, cultivated in Tåstrup for investigation of a potential
seasonal variation in the content of cichoric acid and alkamides.
PAGE 55
The project has run over the latest five years with financial
support from the Danish Research Councils. Within the pro-
ject emphasis has been put on plants with content of fatty
acids, plants with caffeic acid derivatives and plants with iri-
doids, all with potential use in the technical and pharmaceuti-
cal industry directly or after derivatization.
Caffeic acid derivatives are important antioxidants and ma-
jor ingredients of many plants commonly used in herbal reme-
dies. Main emphasis has been given to Echinacea purpurea
in an attempt to give guidelines for production and use in
Denmark. Evidence of the activity of the compounds in
Echinacea is still lacking, and we have ongoing investigations
of the biological activity of the major constituents, cichoric
acid, alkamides and polysaccharides. As a first result we have
verified the activity of cichoric acid as an antioxidant compa-
rable to rosmarinic acid.
Iridoids are compounds of restricted occurrence in the plant
kingdom, often confined to the same taxonomic groups as
contains caffeic acid derivatives, although these are more
widespread. They are very promising as starter material for
the synthesis of pharmacologically active compounds to be
used in the treatment of cancer or HIV. In a taxonomical study
of the genus Plantago we are making use of DNA sequencing
and the chemotaxonomic value of iridoids and caffeic acid
derivatives characteristic for this taxon. Iridoids and caffeic
acids are common in the whole order of Scrophulariales, incl.
Plantaginaceae, with a number of potential medicinal plants.
(Per Mølgaard, Kim Itenov, Nina Rønsted, Line Sandager,
Søren Johnsen, Line Thygesen and Peter Christensen in col-
laboration with Henrik Franzyk [the Natural Products Group],
Claus Cornett [Department of Analytical and Pharmaceutical
Chemistry]), Søren Rosendal Jensen, [Department of Organic
Chemistry, the Technical University of Denmark] Poul
Flengmark [Danish Agricultural Research Institute, Research
Centre Flakkebjerg] and Leif Skibsted [Department of Food
Chemistry, Danish Agricultural University]).
The ENDOD project for the control of schistosomiasis
transmitting snails
This project is carried out in cooperation with a Zimbabwean
counterpart and the Danish Bilharziasis Laboratory (DBL) and
is dependent on financial support from Danida to DBL. The
aims are to facilitate the cultivation of the Endod plant (Phyto-
lacca dodecandra) and application of the molluscicidal berries
to infected water, in an integrated control of schistosomiasis
(Bilharziasis), a tropical water related disease, where fresh
water snails are crucial for transmission of the parasite.
Control of the intermediate host snails supports the other as-
pects of the general control of schistosomiasis, which affects
more than 200 mio. people in the Tropics.
In the reference period a sociological study of community
participation was completed by a PhD student from Zimbabwe.
His study concerned introduction of the Endod-plant as an
easily grown and locally applied snail control measure. This
should offer a low cost - low technology self help device in
combination with chemotherapy, improved water and sanita-
tion, and health education in the control of schistosomiasis.
See also: www.dfh.dk/activities/endod/index.htm.
(Per Mølgaard in collaboration with Ebba Holme Hansen
[Department of Social Pharmacy), Peter Furu [Danish
Bilharziasis Laboratory], Addmore Ndekha [Blair Research
Laboratory, Harare, Zimbabwe]).
Ethnopharmacological studies of plants
from Réunion Island
This project investigates plants used in traditional medicine in
Réunion Island and plants related to traditionally used plants.
Recent studies include three endemic Melicope species (syn-
onym Euodia), M. borbonica, M. coodeana and M. obscura
selected on basis of their biological activity in preliminary
screening assays. The three species showed significant in vit-
ro antibacterial, antifungal, antimalarial and/or antioxidative
activities.
From the leaves of M. borbonica, 15 constituents have
been isolated and identified. The antifungal activity could be
assigned to xanthoxyline and scoparone, present in very high
concentrations, as well as to limettin and 1,4-epidioxy-bis-
abola-2,12-diene. These compounds showed inhibition of the
in vitro growth of Candida albicans and Penicillium expansum.
The two major methoxyflavones from the leaves inhibited the
NF-�B transcription factor.
Three flavones, 5,7-dihydroxy-3,8-dimethoxy-3’,4’-methyl-
enedioxyflavone (1), 5,7-dihydroxy-3,6,8-trimethoxy-3’,4’-
methylenedioxyflavone (2) and 5,7-dihydroxy-3,6,8,3’,4’-pen-
tamethoxy-flavone, out of five isolated from M. coodeana
were new structures and the presence of the unusual methyl-
enedioxyflavones in this species is of chemotaxonomic impor-
ANNUAL REPORT 2000–2001
PAGE 56
New compounds from Melicope coodeana.
1: R = H
2: R = OCH3
tance. From M. coodeana compounds with antimalarial and
antioxidative activity have been isolated but the structures not
finally elucidated.
Four compounds with antibacterial and antifungal activity
have been isolated from M. obscura.
(Anne Adsersen, Ulla Wagner Smitt, Henrik Toft Simonsen in
collaboration with Jerzy W. Jaroszewski [The Natural Products
Group]), Dominique Strasberg [University of Réunion]).
Secondary plant compounds in Arctic plants
This project is linked to ITEX - the International Tundra
Experiment
(http://www.systbot.gu.se/research/ITEX/itex.html), which is a
circumpolar co-operation with stations at more than 20 sites
in the arctic area. By observation and manipulation with se-
lected, wide spread plant species, the aims are to anticipate
the reaction of these plants and the environment they occur
in to an eventual global climate change. The observations and
manipulations are carried out after the same instructions at all
sites.
Our contribution mainly concerns plant secondary con-
stituents, and the effect on these compounds of a change in
weather conditions in the Arctic. These compounds are of im-
portance in relation to protection against herbivory and are
probably affected by increased temperatures, which may lead
to a change in relative reproductive success. The main em-
phasis is put on chemical compounds in Salix arctica,
Papaver radicatum, Cassiope tetragona, and plant phenolics
in general. As arctic plants have not been thoroughly investi-
gated, we have so far been able to identify two genuine com-
pounds new to plants.
(Per Mølgaard, Karen Christensen, Anette Lauritzen, Jakob
Tjelum, in collaboration with Claus Cornett [Department of
Analytical and Pharmaceutical Chemistry]).
Optimisation of the antiplasmodial effect
of the natural product licochalcone A
The antiplasmodial and antileishmanial activities of Chinese
licorice roots (Glycyrrhiza inflata) has been related to the con-
tent of licochalcone A. Orally administration of this compound
to mice infected with malaria clears the infection efficiently but
only in relatively high doses. This drawback might be related
to a poor absorption of the drug from the stomach or guts.
The structure of licochalcone A enables syntheses of a
large numbers of analogues and thereby facilitates medicinal
chemistry studies. A positive relation between the chemical
structure and biological activity has previously been proven (a
QSAR model) but the model is only valid for poorly water-sol-
uble analogues. A number of water-soluble analogues were
prepared and their ability to kill malaria parasite in vitro were
determined. A poor variation in their biological activities pre-
vented development of a QSAR-model.
(Klaus Jensen, Søren Brøgger Christensen).
Structure and pharmacology of natural products
Structure elucidation and biological characterisation of natural
products is a mainstream activity of the Natural Products
group. The research is currently focused on antiprotozoal
compounds. The group’s own biological laboratory performs
drug-sensitivity assay using various strains of Plasmodium
parasites as well as assays for cytotoxic activity using wild
type and multidrug-resistant human cancer cell lines, available
via collaboration with National Cancer Institute, Bethesda,
USA. Studies of effects of natural products on Plasmodium
falciparum involve investigations of their action on erythrocyte
membrane, as it was recently discovered, that incorporation
of various compounds into the lipid bilayer of erythrocytes, in
which the malaria parasites are cultured, inhibits indirectly the
parasite growth and invasion. This effect appears as a false
positive result in the in vitro assay. Further studies of nature of
the effect of erythrocyte membrane modifications on parasite
growth are in progress.
Studies of phytochemical and pharmacological effects of
natural products involve investigations of alkaloids from Apo-
cynaceae, Asclepiadaceae, Periplocaceae and Flacourtiaceae.
DEPARTMENT OF MEDICINAL CHEMISTRY
PAGE 57
Cassiope tetragona, a dwarf shrub from Disko Island in Westh Greenland.
The shoots contain a great variation in essential oil, and several benzoic
acid derivatives of which a methyl ester is new from plants.
During the period covered by this annual report, many novel
phenanthroindolizidine alkaloids, cytotoxic at the nanomolar
level, have been identified. Iranian Perovskia species have
been identified as a new source of tanshinones, clinically use-
ful natural products originally isolated from the
Chinese drug dan-shen. Several highly leishmani-
cidal, novel isoflavans have been isolated from
Smirnowia species. Novel terpenoids belonging
to malabaricane and aromadendrane series have
been identified from Apocynaceae and Flacour-
tiaceae, respectively.
The core-activity of the group is NMR and a
number of NMR spectroscopic studies have
been carried out. These include conformational
studies of alkaloids using dynamic NMR, use of2H NMR in biosynthetic studies (with Nina
Rønsted), use of 31P NMR to characterise influ-
ence of ischemia upon composition of brain
phospholipids (with Harald Hansen, Department
of Pharmacology), use of pulsed-gradient spin-
echo NMR to characterise self-diffusion in phar-
maceutical microemulsion delivery systems (with
Mads Kreilgaard, Department of Pharmacy), and
conformational analysis of polar molecules is
aqueous solution (with Peter A. Nielsen and
Tommy Liljefors, Structural Chemistry). An exter-
nal grant will enable a deployment of state-of-
the-art 600 MHz NMR facilities and HPLC-MS-NMR equip-
ment during 2002.
(Jerzy W. Jaroszewski, Dan Stærk, Henrik Franzyk, Jette
Christensen, Hanne Ziegler, Majid Sairafianpour, Thomas
Høgh Jensen, Vicki Clausen, Bogdan Budnik [University of
Odense], Karim Bagherzadeh [Isfahan Research Centre of
Natural Resources, Iran], Henry Hägerstrand [Åbo Akademi
University], Carl Erik Olsen [Royal Veterinary and Agricultural
University], Ulla Wagner Smitt, Anne Adsersen and Henrik Toft
Simonsen [The Pharmacognosy Group], Partick Ekpe [Univer-
sity of Ghana], Lise Bolt Jørgensen [University of Copen-
hagen], Lars Hviid [Copenhagen University Hospital], Elin S.
Olafsdottir [University of Iceland], Hellen Oketch Rabah
[University of Nairobi]).
Synthesis of analogues of polyamine wasp toxins
Through the development of ligands with a potent and specif-
ic interaction with receptors it is possible to acquire knowl-
edge about the structure and function of the receptors even
in cases where the three-dimensional structure of the recep-
tor is not available. This applies to many membrane-bound
receptors in the central nervous system (CNS). A ligand-type
which is of our particular interest is the group of polyamine
spider and wasp toxins, which have been shown to be non-
competitive inhibitors of ion channel coupled glutamic acid
and acetylcholine receptors. In general these polyamine tox-
ins, called philanthotoxins, are built from three different sec-
tions (depicted below as sections 1-3): a polyamine moiety,
an amino acid, and an acyl moiety.
ANNUAL REPORT 2000–2001
PAGE 58
NMR spectroscopy plays an important role in the research of the Department.
In a preliminary hypothetical model
for the binding of philanthotoxins
(see figure) it was suggested that
these compounds block the ion
channels due to an electrostatic
binding to ionized carboxylic acid
residues in the transmembrane por-
tion of the receptor, and via hy-
drophobic interactions of the amino
acid side chain and acyl chain with
the outer part of the receptor.
Polyamine toxins have been shown
to exhibit a protective effect on
nerve cells, and therefore are inter-
esting as leads in medicinal chem-
istry research towards treatment of
neurodegenerative diseases. It was
previously shown, that the polyamine
chain is essential for activity on glu-
tamate receptors, whereas the inner
amino functionalities may be omitted
in compounds interacting with
acetylcholin receptors.
The present research is concerned with the design and
synthesis of novel conformationally restricted apolar head
groups (i.e. sections 2 and 3). These are then used in parallel
solid-phase synthesis of compounds with improved biological
activity as compared to natural philanthotoxins. Also, novel
sequential solid-phase methods for synthesis of the poly-
amine part are being developed. Here the main effort is to
obtain polyamines, in which N-alkylated, �- or �-alkyl substi-
tuted amines have been incorporated. This requires develop-
ment and optimisation of novel synthetic methods, which
subsequently will allow a systematical study of structure-ac-
tivity relationships in much more diverse libraries of analogues
of polyamine toxins than those investigated previously. The
use of computational methods to correlate the structure of
the apolar head groups with the observed receptor affinity is
currently under consideration for future synthetic analogues.
The tests regarding receptor binding is currently performed in
co-operation with University of Nottingham, United Kingdom.
(Henrik Franzyk, Jerzy W. Jaroszewski, Malene Ryborg
Jørgensen, Christian Adam Olsen, Povl Krogsgaard-Larsen
[The Neuromedicinal Chemistry], Kristian Strømgaard
[Columbia University, New York], Kim Andersen [Lundbeck
A/S], Peter N. R. Usherwood and Ian Mellor [University of
Nottingham]).
Protein modelling and ligand design
by computational methods
By using a combination of computational methods the molec-
ular events associated with many biomolecular processes can
be studied. The availability of experimentally determined 3D-
structures of proteins and ligand-protein complexes makes it
possible to directly study the details of molecular recognition
and perform so-called structure-based computer-aided ligand
design. Even when the detailed structure of the receptor or
enzyme is not known, it is often possible by molecular mod-
elling to construct reliable three-dimensional models, which
allows important issues like activity, selectivity and resistance
to be studied. In cases where only pharmacological data for a
set of ligands are available, 3D-pharmacophore models and
3D-QSAR models which describe important requirements for
the interactions between the ligands and a particular receptor
or enzyme may be developed.
A number of enzymes and ligand-binding domains of re-
ceptors have been studied in order to identify the molecular
features responsible for affinity, selectivity and in some cases
also resistance. One of the enzymes we have studied is ma-
trix metalloproteinase (MMP). Human MMP’s have been found
to be involved in many different disease states, e.g. arthritis,
cancer and osteoporosis. In these diseases, an imbalance is
observed between the MMP’s and their natural inhibitors, and
accordingly, it is desirable to be able to selectively inhibit the
different MMP’s. Key differences have been identified between
several of these enzymes. New methods for selection of pos-
sible binding modes (conformations) and subsequent predic-
tion of their relative binding strength have been developed
based on multivariate statistics. These methods have been
extensively evaluated on a large and structurally diverse set of
DEPARTMENT OF MEDICINAL CHEMISTRY
PAGE 59
Computational methods are important in structure determination.
A substituted flavone fitted to a pharmacophore
model for the benzodiazepine site of the GABAA re-
ceptor. The pharmacophore model has been used
for the design of the compound which displays high
affinity for the receptor with a Ki value of 0.9 nM.
S1-S5 represent areas occupied by the receptor.
H1 and H2 are hydrogen bond donating receptors
sites, whereas A2 is a hydrogen bond accepting
site. L2 denotes a lipophilic cavity.
ligand-macromolecule complexes. The MMP project is carried
out in collaboration with Dr Inge Thøger Christensen, Novo
Nordisk A/S.
Studies on ligand-protein interactions have been performed
for two novel anti-cancer targets MetAP-2 (methionine
aminopeptidase) och VEGF (the vascular endothelial growth
factor) aiming at the design of new ligands which may be de-
veloped into anti-cancer drugs. These studies have been
done in collaboration with Leo Pharmaceuticals.
On the basis of the availability of three-dimensional struc-
tures for the ligand binding domain of an ionotropic glutamate
receptor (iGluR2) in complex with various ligands, a number
of studies have been performed aiming at an understanding
of subunit/subtype selectivity and the design of new
subunit/subtype selective ligands. These studies have in par-
ticular focused on the role of water molecules in the ligand
binding site for the ligand binding mode as well as for ligand
affinity and selectivity. Studies along these lines have also
been performed for metabotropic glutamate receptors on the
basis of the experimentally determined structure of the ligand-
binding part of the mGluR1 receptor. Collaborators in the glu-
tamate receptor projects have been Professor Arne Schousboe,
Department of Pharmacology, the Protein Crystallography and
the Neuromedicinal Chemistry Groups at the Department of
Medicinal Chemistry and Prof. Guiseppe Campiani, Siena,
Italy.
3D-pharmacophore models have successfully been used
for the design of novel high-affinity ligands for the GABA and
benzodiazepine sites of the GABAA receptor. Pharmacophore
models for subtypes of neurokinin receptors (NK1 and NK2)
have been developed and, addition, for all subtypes of the
�1-adrenoceptor. Ligand design on the basis of these models
have been initiated.
The pharmacophore model for the benzodiazepine site of
the GABAA receptor has been used for database searches
and a number of new interesting lead compounds have been
identified. These studies have been performed in collabora-
tion with H. Lundbeck A/S, NeuroSearch A/S, Dr Ingrid
Pettersson at Novo Nordisk A/S, Professor Olov Sterner,
University of Lund and Professor Mogens Nielsen.
(Tommy Liljefors, Anders Hogner, Jeremy Greenwood, Anne
Techau Jørgensen, Anders Poulsen, Thomas Balle, Gitte
Elgaard Terp, Marie-Louise Waagensen, Kasper Harpsøe,
Flemming Steen Jørgensen).
Pharmaceutically important physico-chemical properties
The oral bioavailability of a drug compound is an extremely
complex property influenced by factors like absorption, distri-
bution, metabolism and excretion (ADME properties).
Solubility is one of the key factors determining absorption,
and accordingly prediction of aqueous solubility has become
a major issue in the drug development process.
New models for prediction of aqueous solubility and several
other ADME properties have been developed and extensively
compared with models previously reported in the literature.
The purpose of these studies is to develop tools, which make
PAGE 60
ANNUAL REPORT 2000–2001
Three-dimensional model of acetyl salicylic acid coloured according to
atom type. The water-accessible surface is shown as a semi-transparent
cloud around the molecule.
it possible to determine the ‘drug-likeness’ of compounds pri-
or to synthesis.
Solubility is influenced by solid phase properties, e.g.
molecular structure and crystal packing, as well as by exter-
nal factors like temperature, pH and ionic strength. The crys-
tal packing is a fine balance between many weak and
stronger intermolecular contacts, but unfortunately, crystal
structures are generally not predictable. Projects have been
undertaken in order to achieve improved understanding of the
relationships between solid phase properties such as solubili-
ty and compressibility on one side and the actual crystal
packing on the other side. A series of substituted benzoic
acid salts have been analysed in order to achieve insigth in
the effect of structural parameters on the formation of low
solubility salts, and a series of parabenes have been analysed
for the structural effect on elasticity and compressibility. The
ultimate goal is to be able to predict the solid phase proper-
ties and to design new compounds with optimal characteris-
tics.
These projects involve collaborations with Professor Claus
Selch Larsen at the Department of Analytical and
Pharmaceutical Chemistry, Professor Sven Frøkjær and
Professor Henning Gjelstrup Kristensen at the Department of
Pharmacy and Dr Inge Thøger Christensen, Novo Nordisk
A/S.
(Karla Frydenvang, Tommy Liljefors, Birthe Jensen, Jørgen
Bonefeld Kristensen, Flemming Steen Jørgensen).
Structural studies of CNS proteins by X-ray crystallography
An increased knowledge on three-dimensional structures of
proteins is necessary to fully understand their function at a
molecular level. The protein crystallography group is mainly
focusing on three types of CNS proteins: Ionotropic gluta-
mate receptors (iGluRs), neural cell adhesion molecule
(NCAM), and �-synuclein. iGluRs and NCAM are membrane-
DEPARTMENT OF MEDICINAL CHEMISTRY
PAGE 61
Water molecules in contact with the surface of crystalline urea.
X-ray structure of the ligand-binding domain of GluR2 in complex with the
agonist (S)-Thio-ATPA.
Crystallisation and evaluation of crystals
are fundamental steps in the structure
determination of proteins by X-ray
crystallography.
bound receptors involved in a series of important processes
within the central nervous system. �-synuclein is a brain pro-
tein, which plays a role in neurodegenerative diseases such
as Parkinsons and Alzheimers disease.
Within the glutamate receptor project, we have so far fo-
cused on the ligand-binding domain of GluR2 in complex with
different AMPA receptor agonists and antagonists. Several
structures of complexes have been determined providing a
wealth of information on ligand binding and receptor activa-
tion. The structures of GluR2 in complex with ligands show
different binding modes for the ligands and disclose domain
movements taking place upon ligand binding. Expression and
purification of other receptor subunits has been initiated to
address subtype selectivity.
In the NCAM project, it is our goal to stepwise build up the
whole extracellular part of the receptor by structure determi-
nations of fragments of NCAM, and to determine structures
of NCAM in complex with heterophilic binding partners. This
year, we determined the structure of NCAM-IgI-II-III, and the
structure has allowed us to put forward reliable models for
both NCAM cis and trans interactions, reflecting interactions
of molecules on the same cell and on opposed cells. NCAM-
IgI-II-III-IV has recently been crystallised, and co-crystals of
NCAM-IgI-II and sucroseoctasulphate have been obtained to
address the question whether homophilic and heparin binding
can occur simultaneously.
�-Synuclein is a 14 kDa protein, which belongs to a family
of natively unfolded proteins without, or with very little, sec-
ondary structure elements. Different crystallisation conditions
and various additives are being investigated in order to trigger
the protein, as well as two mutants thereof, to fold and crys-
tallise. Folding is probably triggered by binding to its biologi-
cal target, as well as by polymerisation (fiber formation).
In addition, the structures of three peptide nucleic acids
(PNAs) have been determined. PNA analogues are potential
antisense/antigene drugs. All projects are performed in col-
laboration with both national and international collaborators
from universities and industry.
(Anders Hogner, Christina Kasper, Jette Sandholm Kastrup,
Nikolaj Kulahin, Ingrid Kjøller Larsen, Marie-Louise Lunn,
Bettina Bryde Nielsen, Anja Kallesøe Pedersen, Britt
Petersson, Vladik Soroka, Lise Baadsgaard Sørensen).
GABAA receptor ligands and GABA uptake inhibitors
The GABAergic neurotransmitter system involves a number of
synaptic processes and mechanisms, which have been stud-
ied pharmacologically and constitute potential therapeutic tar-
gets. In continuation of previous projects in this field, the de-
sign and development of ligands for the GABAA receptor and
the GABA uptake system have been of primary interest.
The project on GABAA receptor ligands has been continued
in close collaboration with Professor Tommy Liljefors and his
group. According to a previously proposed pharmacophore
model for GABAA receptor agonists, a receptor cavity in the
vicinity of the 4-position of the 3-isoxazolol ring in 4-PIOL, a
low-efficacy partial GABAA agonist, exists. To explore the di-
mensions and other properties of the receptor cavity, a num-
ber of analogues of 4-PIOL, in which the 4-position of the 3-
isoxazolol ring is substituted by different groups, has been
synthesised. This study has transformed 4-PIOL into the
PAGE 62
ANNUAL REPORT 2000–2001
highly potent GABAA antagonist 1. During the past year, 1
has been developed into a series of very potent GABAA an-
tagonist including compound 2, which in functional assays is
even more effective than 1.
Similar structural changes have been made for the isothia-
zolol analogue of 4-PIOL, thio-4-PIOL, which has been shown
to possess markedly higher efficacy than 4-PIOL. Although
the chemistry of 3-isothiazolols is complex, a series of thio-4-
PIOL analogues has been synthesised and shown to be sig-
nificantly more potent than the 3-isoxazolol analogues.
In collaboration with professor Arne Schousboe and his
group at the Department of Pharmacology a number of very
significant and, from a therapheutic point of view, potentially
important results on the GABA uptake project have been ob-
tained. The cyclic amino acid, nipecotic acid, was discovered
by the NeMe group as a specific GABA uptake inhibitor some
years ago and subsequently converted into the antiepileptic
drug, tiagabine, by incorporation of the lipophilic DTB group
as an N-substituent at Novo Nordisk A/S. In the NeMe group
N-Me-exo-THPO was subsequently syn-
thesised and shown to be a glia-selective
GABA uptake inhibitor. The DTB-ana-
logue of N-Me-exo-THPO has now been
fully characterised as a very potent GABA
uptake inhibitor showing a unique phar-
macological profile different from that of
tiagabine. Due to a very complex chem-
istry required for the synthesis there has
been no further development of this com-
pound.
Very recently the isomeric amino acids
3 and 4 have been shown to have weak
GABA uptake inhibitor effect. By introduc-
tion of lipophilic substituents, both 3 and 4 were converted
into GABA uptake inhibitors showing yet another unique
pharmacological profile. This effect of the analogues of 3 and
4 is now under further exploration in animal behavioural stud-
ies in order to elucidate their therapeutic potential.
The projects described are interdisciplinary collaboratory
projects involving other research groups at DFH and in the
industry.
(Titi Akinleminu, Rasmus Prætorius Clausen, Bente Frølund,
Karla Frydenvang, Povl Krogsgaard-Larsen, Christian
Madsen, Lotte Olsen, Dorte Seir Petersen, Tine Bryan
Stensbøl).
Excitatory amino acid receptor ligands
The central excitatory amino acid neurotransmitter, glutamic
acid (Glu), operates through a large number of receptor sub-
types divided into two groups, the ionotropic (iGlu) receptors
and the metabotropic receptors, the latter group belonging to
the superfamily of 7-TM receptors. The iGlu receptors com-
prise the NMDA, the AMPA (GluR1–4), and the kainic acid
(GluR5–7 and KA1–2) receptors. In recent years the research
has been focused on the AMPA and kainic acid subgroups of
receptors.
During the past one year period a num-
ber of research projects related to
bioisoster replacement of carboxy groups
have been accomplished. As part of an
ongoing project using 3-isoxazolols as
carboxy group bioisosteres, new ana-
logues of AMPA containing aromatic sub-
stituents in the 5-position of the 3-isoxa-
zolol ring, exemplified by the pyrazinyl
analogue (1), have been synthesized in an
effort to further map out structural re-
quirements for AMPA receptor agonist
activity. In connection with these studies,
a new and versatile method for the
DEPARTMENT OF MEDICINAL CHEMISTRY
PAGE 63
Proposed bioactive conformation of 1 placed in a pharmacophore model
for GABAA agonists . The tetrahedron indicate areas occupied by the
receptor.
Nipecotic acid
Thio-4-PIOL4-PIOL
1 2
DTB-N-Methyl-exo-THPON-Methyl-exo-THPO
3 4
preparation of 5-substituted 3-isoxazolols via acylated
Meldrum’s acids has been developed.
In another project 1-hydroxyazole-containing �-amino acids
have been synthesised and pharmacologically evaluated.
These studies have identified the 1-hydroxypyrazole (2a and
2b) and the 1-hydroxy-1,2,3-triazole (3a and 3b) analogues
as new and useful bioisosteres at iGlu receptors and at Glu
transporters. Molecular modelling studies using a published
crystal structure of the ligand binding site of GluR2 have
shown that these compounds can bind to the receptor in an
“AMPA-like mode” making the same favorable contacts as
AMPA and not entering sterically forbidden zones.
Important progress has also been achieved in projects us-
ing the 3-isothiazolol ring system as a carboxy group
bioisostere at Glu receptors. In this regard regioselective lithi-
ation and functionalisation of 3-(benzyloxy)isothiazole has
been carefully investigated, and these studies has led to the
preparation of thioibotenic acid, the sulfur analogue of the
neurotoxic natural product ibotenic acid. The pharmacological
characterisation of thioibotenic acid carried out so far shows
interesting agonist activity at iGlu as well as mGlu receptors.
The 3-hydroxy-1,2,5-thiadiazole ring system, which forms
the distal acidic part of the �-amino acid TDPA, is structurally
closely related to the 3-isothiazolol ring present in thioibotenic
acid. Pharmacological studies on the enantiomers of TDPA
have revealed a complex and interesting pharmacological
profile. In addition to a moderate agonist activity at group I
mGlu receptors, (S)-TDPA selectively interacts with the Glu
transporter EAAT2, and shows agonist activity at AMPA re-
ceptors. In contrast, (R)-TDPA shows a more clear pharma-
cology, being a selective AMPA receptor agonist
with almost the same affinity as (S)-TDPA. The
transporter activity and the unusually low stereose-
lectivity at AMPA receptors observed for TDPA
makes the 3-hydroxy-1,2,5-thiadiazole a unique
carboxy group bioisostere.
ACPA and its demethyl analogue, which are ana-
logues of AMPA, have been resolved using chiral
HPLC. X-ray crystrallography has been used to es-
tablish the absolute configuration of the resolved
enantiomers. The configurational assignment ob-
tained from this X-ray study has been supplement-
ed by an asymmetric synthesis of (S)-ACPA and an
X-ray analysis of a derivative of (S)-ACPA.
Pharmacological studies have revealed that the po-
tent AMPA receptor agonist activity of ACPA resides
exclusively in the S-enantiomer, and that both
enantiomers of demethyl-ACPA are relatively weak
AMPA receptor agonists, (S)-demethyl-ACPA being
the most potent.
In continuation of ongoing projects, the crystal
structures of the potent GluR5 receptor agonists,
ANNUAL REPORT 2000–2001
Chemical structure of selected ionotropic Glu receptor ligands.
PAGE 64
Compound 3b docked into the binding site of GluR2. Selected hydrogen bonds are shown in black.
ATPA and thio-ATPA, have been solved. Together with quan-
tum chemical calculations these studies show, that whilst the
3-isoxazolol tautomer of ATPA predominates in all phases, the
3(2H)-isothiazolone tautomer of thio-ATPA predominates in
the crystal structure and most likely in weakly acidic aqueous
solution.
Furthermore, hybrid analogues of the kainic acid receptor
agonists (2S,4R)-4-methyl-Glu and ATPA (exemplified by 4)
have been prepared and show highly selective GluR5 recep-
tor affinity.
Many of the mentioned projects have been performed in
close collaboration with other research groups at the Royal
Danish School of Pharmacy, in particular structural chemists
and molecular pharmacologists and other research groups in
the pharmaceutical industry.
(Hans Bräuner-Osborne, Lotte Brehm, Lennart Bunch,
Rasmus P. Clausen, Bente Frølund, Karla Frydenvang, Mette
Guldbrandt, Mette B. Hermit, Tommy Nørskov Johansen, Povl
Krogsgaard-Larsen, Ulf Madsen, Birgitte Nielsen, Frank Sløk,
Tine B. Stensbøl, Ulrik Svane Sørensen, Jón Valgeirsson,
Stine B. Vogensen).
Family C 7TM receptors
Human G-protein coupled receptors are
generally divided into three families
(Family A, B and C) based on their re-
semblance in amino acid sequence. All
G-protein coupled receptors span the
cell membrane seven times and are
thus also called 7 transmembrane
(7TM) receptors. Family C, which con-
sists of eight glutamate (mGlu1-8), two
GABAB and one calcium-sensing (CaR)
receptor, has traditionally been charac-
terised by a unusually large amino-
terminal ligand binding domain (see
figure).
The NeMe group has developed
pharmacological assay for the mGlu,
GABAB and CaR receptors that enable
us to study compounds synthesised in
the NeMe group and by collaborators.
In this way new potent ligands have
been developed which display selecti-
vity for subsets or individual receptor
subtypes.
Based on mutational studies we have
been able to identify amino acids in the amino terminal domain,
which are directly involved in agonist binding. The recent pub-
lication of the X-ray crystal structure of the ligand binding do-
main of the mGlu1 receptor has led us to generate computer
models of the remaining seven mGlu receptors. These models
DEPARTMENT OF MEDICINAL CHEMISTRY
Model of the extracellular ligand binding domain of a metabotropic gluta-
mate receptor complexed with glutamate.
Single crystal of (S)-demethyl-ACPA used in the X-ray analysis together
with a perspective drawing of the molecule based on the analysis.
PAGE 65
are being tested by mutagenesis with the aim of increasing
our understanding of ligand selectivity.
Numerous studies have shown that the family C receptors
are homo- or heterodimers. Based on the X-ray crystal struc-
ture it has been proposed that agonist binding leads to acti-
vation by bringing the two 7TM domains in the dimer closer
together. This hypothesis has been tested by use of a tech-
nique called bioluminescence resonance energy transfer
(BRET).
The NeMe group has recently cloned a new group of previ-
ously unknown family C receptors. In contrast to previous as-
signed family C members, this new group is characterised by
a short amino terminal domain. The expression pattern and
cellular localisation of the new receptors has been determined
(see figure). 1000 putative ligands have been screened in a
FLIPR high-throughput assay, but unfortunately no active lig-
ands have yet been identified.
(Hans Bräuner-Osborne, Anders A. Jensen, Mette B. Hermit,
Petrine Wellendorph).
New synthetic methodologies
The synthesis group has been working on several new syn-
thetic methods of importance in medicinal chemistry. Regio-
selective introduction of functional substituents and cross-
couplings have been performed with complete control in all
positions in 1-hydroxypyrazole and pyrazole. The reactions
have been combined with new anionic cyclisation reactions
which have provided several new ring systems and ring sys-
tems of significant interest in medicinal chemistry. Similar re-
actions have been performed in the imidazole and thiophene
series.
Effective methods for the preparation of 2-substituted
phenylboronic esters have been developed. These com-
pounds serve as synthons and have a enormous potential in
synthesis and medicinal chemistry allowing connection of two
functional aryl groups and construction of rings by anionic
cyclisation.
Cross-coupling reactions have also been employed by the
construction of tamoxifen analogues with improved proper-
ties. Subsequent anionic cyclisation have given a highly active
analogue with constricted conformation.
A broafly applicable synthon for preparation of phenyl-
glycines and heterocyclic analogues has been developed and
its versatility demonstrated by preparation of a series of new
or difficult accessible amino acids. A protocol for preparation
of heterocyclic phenyl analogues has also been established.
Several of the new compounds are under biological testing.
New drug substances have been coupled
to peptide carriers in order to improve the
transport of the drug through the intestinal
barrier. New methods for construction of li-
braries of privileged structures using solid
phase chemistry have been initiated.
New methods for isotop labeling of drug
metabolites and positron emitting drug
tracers are under development.
Development of methods for preparation of
lipid conjugates for drug targeting is in pro-
gress.
(Mikael Begtrup, Patrizia Cali, Peter Elm,
Jørgen Eskildsen, Jesper Kristensen, Uffe
Larsen, Jan Pawlas, Rune Severinsen,
Martin Wenckens, Niels Østergaard og Per
Vedsø).
ANNUAL REPORT 2000–2001
Confocal mi-
croscopy image of
cells expressing an
orphan 7TM recep-
tor fused to green
fluorescent protein
(GFP).
PAGE 66
DEPARTMENT OF MEDICINAL CHEMISTRY
PAGE 67
Department ofPharmaceutics
SPHERE OF INTEREST
The Department of Pharmaceutics deals with the formulation,
processing and quality assurance of drug products, i.e. the
objectives involved in bringing a drug substance into an effec-
tive and safe dosage form. Further, the activities include how
to administer the drug product safely and optimise the effect
for the individual patient. The scientific and teaching objec-
tives are therefore dosage form design, processing of dosage
forms, quality assurance, clinical pharmacy and pharmaco-
therapy.
The formulation design of drug products takes its starting
point in the chemical, physico-chemical, pharmacokinetic and
pharmacodynamic properties of the drug substance, the
route of administration and the manufacturing method. The
stability of the substance as such and in formulation, the
choice of excipients and different approaches to overcome
the transport across restrictive biological barriers are objects
of interest. Chemical, physical and pharmaceutical-technical
methods for evaluation of drug formulations are necessary
tools.
The Department participates in an extramural research cen-
tre, the Centre for Drug Design and Transport. Professor Sven
Frøkjær is the head of the centre, established as a four-year
programme to be terminated on 1 November 2001.
Professor Henning G. Kristensen is chairman of the European
Pharmacopoeia Commission, which is important to the func-
tioning and development of the Department.
RESEARCH
The four main areas of research at the Department of
Pharmaceutics are:
Pharmaceutical formulation: Formulation of drug products
taking into consideration the physical, chemical and pharma-
cokinetic and pharmacodynamic properties of the drug sub-
stance, the route of administration, the processing method
and clinical use of the product
ANNUAL REPORT 2000–2001
Head of Department:
Associate professor Margrethe Rømer Rassing, PhD, MSc (pharm.)
PAGE 68
Civil servants from The Ministry of Education and The Ministry
of Research visited the department in November 2000.
Drug delivery: Design of drug delivery systems actively con-
trolling and optimising the absorption of drug substance
and/or its transport in the living organism to the site of action
Processing technology: Unit operations applied in the pro-
cessing of drug products and the influence of the method
selected on formulation design
Clinical pharmacy: Optimisation of the therapeutic result of a
medication taking into consideration the biopharmaceutical
profile of the drug product and its pharmacokinetic and phar-
macodynamic properties
The character of the research is interdisciplinary and integrat-
ed. Projects are typically carried out in research groups of
scientists from various research groups established at the
Department of Pharmaceutics and from other university de-
partments, university hospitals and hospital pharmacies and
the pharmaceutical industry.
The number of PhD students at the Department has grown
steadily in recent years. In 2001 approximately 35 PhD stu-
dents were supervised by staff members of the Department
of Pharmaceutics in collaboration with supervisors from the
pharmaceutical industry. The involvement of adjunct profes-
sors is very important in this context. At present adjunct pro-
fessors are managing director Ole Wørts, Glatt Norden, Dr.
Vagn Handlos, head of the State University Hospital Pharmacy,
Professor Dr. Gert Storm from the University of Utrecht in the
Netherlands and Professor, Dr. Hans Lennernäs, Uppsala
University, Sweden. Professor, Dr. Hans Peter Merkle, ETH
Zurich, Switzerland, has been appointed adjunct professor in
2001.
The bulk of PhD scholarships are based on external fund-
ing, in particular from the Danish pharmaceutical industry in
keeping with contracts established on drug formulation train-
ing and the Centre for Drug Design and Transport. The
agreed industrial funding is, however, running out. The num-
ber of PhD students will therefore decline dramatically during
the next two years unless we are able to attract new funding.
The strategy of the Department of Pharmaceutics is to
strengthen international relations by exchanging PhD stu-
dents and staff members with university departments abroad.
Consequently nearly all PhD students visit university depart-
ments abroad as part of their PhD programme. The Depart-
ment also attaches great importance to hosting foreign PhD
students and scientists to establish collaborative research.
PHARMACEUTICAL FORMULATION
The formulation of low soluble drug substances intended for
oral delivery has been subject to intensive research in recent
years. Current projects focus on the effects of luminal liquids
on the dissolution/solubilisation of drug substances, lymphatic
transport of lipophilic substances and formulation of lipid-
based drug delivery systems. The research is conducted in
collaboration with the Danish pharmaceutical companies,
Dumex Alpharma A/S, Leo Pharmaceuticals A/S and H.
Lundbeck A/S, as well as with scientists at universities
abroad. A new research consortium within the Øresund re-
gion was established in 2001. The Department participates in
a project on in vivo in vitro correlations of lipid-based formula-
tions. External partners are Lund University, Sweden, Camu-
rus, Sweden, AstraZeneca R&D Lund, Sweden and Nycomed
Pharma, Denmark.
In vitro methods suitable for the screening of drug sub-
stances and their formulations have been established on the
basis of aqueous media simulating the compositions of the
gastro-intestinal liquids in fasted and fed states. Further, a
lipolysis model for dissolution testing and evaluation of effects
of fat-enriched diet on oral absorption has been established.
The model is subject to evaluation in collaboration with Aventis
Pharma, Frankfurt. An increasing number of new drug sub-
stances are highly lipophilic and thus prone to lymphatic
DEPARTMENT OF PHARMACEUTICS
The attachment of adjunct professors has become very important. Dr. Hans Lennernäs, Uppsala
University was appointed in September 2000.
PAGE 69
transport. Animal models (rats, dogs) for studies of lymphatic
transport have been established and applied in investigations
on the role of triglycerides in systemic absorption.
Investigations on lipid-based formulations, which were con-
cluded in 2001, concern the development of dry emulsions
and SEDDS for oral delivery of low soluble drugs and the use
of tocopherols as a vehicle for low soluble drugs.
Lipid-based formulations for parenteral use are also subject
to research. The projects concern the role of structured lipids
in parenteral drug delivery and emulsion technology. The aim
is to investigate the possibilities of incorporating hydrophilic
as well as lipophilic drug substances into the lipid-based vehi-
cles.
Particulate drug delivery systems are the subject of two
projects carried out in collaboration with Cheminova and
Pharmexa.
DRUG DELIVERY
The research within the area of Drug Delivery is focused on
drug transport across biological membranes and studies on
lipid-based drug delivery systems.
Macromolecules such as peptides, proteins, and oligonu-
cleotides present a unique pharmaceutical formulation chal-
lenge. The therapeutic application of these groups of com-
pounds is limited by several problems, such as lack of physi-
cal and chemical stability and the lack of optimal physico-
chemical properties for adequate transport across biomem-
branes. Thus, the pharmaceutical sciences face the challenge
of gaining a more basic understanding of transport problems
and developing strategies to solve them.
Access to well-characterized in vitro models to study drug
transport across biological membranes is of the utmost im-
portance. Various models based on tissue as well as cell cul-
ture models are established in the Department, i.e. intestinal,
buccal, and nasal membranes, cornea, and skin, the human
colon cell line, Caco-2, and the human buccal cell line, TR
146. These in vitro models are important tools for obtaining a
more fundamental understanding of the molecular and phar-
maceutical parameters, which are of significance for drug
transport across biological membranes. However, in some
situations the findings from in vitro studies have to be con-
firmed in vivo in order to establish biological relevance. These
studies are usually conducted on mice, rats, or rabbits.
To obtain effective drug therapy, the drug substance must
be able to reach the site of action in a therapeutically active
concentration. Various approaches are taken to optimise the
drug delivery properties of drugs to improve membrane trans-
port and release characteristics. Combining bioreversible
derivation with carrier-mediated transportation has developed
the classic prodrug approach further. Within this area, the
Department is focusing on the potential use of the di-/tripep-
tid carrier as a transporter for drugs with poor membrane
transport characteristics. This research is being conducted in
collaboration with the Department of Medicinal Chemistry.
The development of particulate drug delivery systems
based on liposome technology is also a focus area. These
activities are carried out in collaboration with Professor O. G.
Mouritsen, the MEMPHYS-group, Department of Physics,
University of Southern Denmark.
As more therapeutic proteins are made available, it is es-
sential to formulate these drugs into safe, stable and effica-
cious delivery systems. Our research goal in this area is to
obtain a basic understanding of parameters controlling the
physical stability of proteins in pharmaceutical systems, pri-
marily by investigating the effect of excipients and studying
protein-interface interactions. A Protein Formulation Network
has recently been established in collaboration with a number
of Danish pharmaceutical companies.
In the area of oligonucleotide/DNA drug delivery, the aim is
to develop polymeric and lipid-based drug delivery systems
that can effectively deliver oligonuleotides or plasmid DNA to
the target site. The therapeutic focus within this area is gene
and antisense therapy as well as DNA vaccination.
PROCESSING TECHNOLOGY
The research within processing technology focuses on the
formulation and processing of solid dosage forms intended
for oral administration. Central themes are particle technology,
unit operations and pharmaceutical preformulation. Particle
agglomeration has long been a major research field. The re-
search group is well equipped with various types of mixer-
granulators. Current research concerns melt granulation and
melt pelletisation in high shear mixers, in particular the role of
binder viscosity for the formation and growth of agglomerates.
Other projects deal with the use of melt agglomeration for de-
veloping matrix pellets with predictable dissolution properties,
e.g. the use of solid dispersion technique to increase the dis-
solution rate of low soluble drugs. This research is conducted
in collaboration with Danish pharmaceutical companies, in
particular H. Lundbeck A/S.
Pelletization in rotor-fluidised beds is studied to develop
rapidly disintegrating pellets. The project is conducted in col-
laboration with Glatt Norden and Professor P. Kleinebudde,
University of Halle, Germany.
Compaction of particulate solids into tablets has been the
subject of studies on mathematical modelling. This experi-
mental work is based on the use of a compaction simulator.
Finally, the research group has established research on the
atomisation of aqueous solutions with a view to coating fine
particles and the preparation of inhalable particles. The use of
effervescent atomisation in combination with spray drying is
being investigated with a view to the design of the atomizer.
PAGE 70
ANNUAL REPORT 2000–2001
At a later stage the research will be re-directed towards the
coating of fine particles. Investigations on the preparation of
inhalable particles are being made in collaboration with
AstraZeneca Lund R&D and the University of Lund, Sweden.
CLINICAL PHARMACY
Clinical pharmacy deals with rational pharmacotherapy and
optimising the clinical use of drugs. The main research areas
for the Clinical Pharmacy group concern indicators to evalu-
ate the drug dosing-response relationship, and drug monitor-
ing by clinical pharmacokinetic service. Pain management is
one of the main areas of interests for the group. Opioids are
studied in patients with chronic pain of malignant as well as
non-malignant origin. Paracetamol and other non-steroid anti-
inflammatory drugs (NSAIDs) are studied in patients with
acute pain, children as well as adults. The pharmacokinetics
of prenisolone in the acute phase of the treatment of children
diagnosed with acute lymphoblastic leukemia is another re-
search area of great interest. The group is often involved in
projects concerning the influence of drug formulation and de-
vices on patient compliance and acceptance.
CENTRE FOR DRUG DESIGN AND TRANSPORT
The "Centre for Drug Design and Transport" is an extramural
research centre established in November 1997 as a four-year
programme and therefore terminated in October 2001.
The centre is based on seven Danish research groups and
funded by the Danish Medical Research Council, several
Danish pharmaceutical companies and the participating aca-
demic institutions. Professor Sven Frøkjær is the head of the
centre. See page 26 Research Centres at The Royal Danish
School of Pharmacy.
TEACHING
During the summer of 2001, a major renovation of the De-
partment was finalised and the amount of square meters in-
creased to provide better teaching and research facilities. The
new conditions are very much appreciated by staff and stu-
dents alike.
In the academic year 2000/2001, the Department taught
the introduction to the study of pharmacy, compulsory and
optional courses in pharmacy, supervised students doing their
master’s theses and held PhD courses.
The introduction to the study deals with lectures and tutori-
als in drug formulation and manufacturing and knowledge of
the European Pharmacopoia. Further, demonstrations in how
to prepare e.g. tablets and parenteralia are given.
Students are trained to master drug formulation, drug pro-
duction and evaluation as well as quality assurance. The
compulsory courses combine lectures, tutorials, laboratory
work, written exercises and oral presentations. During the
fourth year of the programme, students carry out a project
within drug formulation and one within drug manufacturing.
The content of the course in drug formulation was revised in
2001, and a different textbook used (Physicochemical Prin-
ciples of Pharmacy). A project entitled "Test of an examination
form for better evaluation of the students’ understanding and
ability to solve more complex pharmaceutical problems" has
been planned and will be carried out in the spring 2002.
Furthermore, the Department of Pharmacy together with the
Department of Pharmacology held a compulsory course in
pharmacotherapy.
The Department also offered elective courses in advanced
drug formulation, industrial production and quality assurance
of pharmaceuticals, validation in the manufacture of pharma-
ceuticals, controlled release, clinical pharmacy, statistical de-
sign of experiments, registration of drugs and seminars and
clinical practice in clinical pharmacy.
The two PhD courses dealt with drug delivery and clinical
evaluation of drug products, respectively. Furthermore, the
DEPARTMENT OF PHARMACEUTICS
PAGE 71
Department made contributions to other PhD courses, e.g.
biological membranes, permeation barriers and drug target-
ing.
The Department of Pharmaceutics supervised 77 students
earning their master’s theses. About half of these students
worked on their theses at national or international pharma-
ceutical production sites or institutes. A number of foreign
students prepared their theses at the Department.
During the past three years, 18 students received their PhD
degree from the Department. Fifteen of the projects in the
field of drug formulation were funded by Danish pharmaceuti-
cal companies, the Danish Research Academy and the
Danish Medical Research Council through the Centre for Drug
Design and Transport. This programme has now been termi-
nated and unfortunately the number of PhD students at the
Department is decreasing. However, 34 people were regis-
tered for the PhD degree programme on 1 January 2002.
SPECIALISATION IN HOSPITAL PHARMACY
The need for specialised training in Hospital Pharmacy has
been acknowledged for several years. To improve the clinical
and scientific skills of hospital pharmacists, the Danish
Society of Hospital Pharmacy Managers in co-operation with
the Royal Danish School of Pharmacy are preparing a new
postgraduate programme. The new programme will focus on
clinical pharmacy –the optimal use of drugs for the benefit of
each patient and society. The curriculum will be
equivalent to one year of courses, although it will
be taught over a longer period of time.
Janne Rømsing, Department of Pharmaceutics, is
head of the Study Board for "Specialisation in
Hospital Pharmacy".
GUESTS AND EVENTS:
Professor Hans P. Merkle, Galenische Pharmazie
ETH, Zürich, has been attached to the department
as assigned professor.
Professor Gert Storm, Department of
Pharmaceutics, Utrecht University, The
Netherlands.
Professor Hans Lennernäs, Department of
Pharmaceutics, University of Uppsala, Sweden.
Dr. Thomas Abberger, University of Innsbruck,
Austria, joined the agglomeration research group
from August 13 to September 7 2001.
David Ilardia, PhD student at the university in
Vittoria, Spain, joined the GISOL research group
from January to July 2001.
Regina Westmeyer, pharmacy student at the uni-
versity in Kiel, Germany, joined the research on par-
ticulate DNA-formulations for a 6 months period from Sep-
tember 2001.
Christina Jimenez, MSc, Barcelona, has joined the GISOL-
group since October 1, 2001.
Minisymposium - NeuroScience PharmaBiotes and Drug
Design and Transport, March 1-2, 2001, Sorø
ADME in Drug Research - Tools for Evaluation and
Prediction of Absorption, Distribution, Metabolism and
Excreation, The Royal Danish School of Pharmacy, June 21,
2001.
World Conference on Drug Absorption and Drug Delivery,
June 18-20, 2001, Copenhagen, Co-chairman: Sven Frøkjær.
Member of the Scientific Programme Committee: Henning G.
Kristensen, Sven Frøkjær
Benzon Symposium - Drug Metabolism: Regulation and
Importance, September 16-20, 2001, Copenhagen.
Member of the organizing committee: Sven Frøkjær
MEMBERSHIP OF EXTERNAL COUNCILS AND BOARDS
Henning Gjelstrup Kristensen is a member of the Academy
for Technical Sciences (ATV), chairman of the Danish
Pharmacopoeia Commission and chairman for its sub-com-
mittee on Pharmacy. In 2001 he was elected chairman of the
European Pharmacopoeia Commission for a period of three
years. He is chairman of the Group of Experts No. 12 (Drug
Dosage Forms) and has the chair for a number of Working
ANNUAL REPORT 2000–2001
PAGE 72
Parties settled under the Pharmacopoeia Commission:
Standard Terms, Powder Characterisation, Inhalations, Water
Qualities, and Methods for the manufacture of sterile prod-
ucts. In 2001 he became a member of the Steering
Committee for the Certification of Suitability of Drug
Substances. Member of WG4 on Dissolution and
Bioequivalence under FIP. Member of WHO Advisory Panel on
Pharmaceuticals. Referee within natural sciences and tech-
nology for the Research Council of Norway. Member of the
editorial board for International Journal of Pharmaceutics.
Member of the scientific board for Viikki Drug Research
Technology Center, University of Helsinki. From 2001,
Sectional Editor of the European Journal of Pharmaceutical
Sciences. He is a member of the scientific committee for the
4th World Meeting on Pharmaceutics, Biopharmaceutics and
Pharmaceutical Technology 2002, the Drug Absorption
Conference, EUFEBS 2001 and the EUFEBS Decennial
Anniversary Conference on Optimising Drug Development,
2001. In 2001 external examiner to assist the peer review of
Schools of Pharmacy in the United Kingdom and a member
of an international panel to review the research at the Faculty
of Pharmacy and Faculty of Medicine, University of Kuopio,
Finland.
Sven Frøkjær is a member of the Danish Academy for
Technical Sciences (ATV), trustee of the Alfred Benzon
Foundation, member of the Danish Medical Research
Council, member of the council for Centre for Advanced Food
Studies (LMC) and other program committees under the
Danish Research Agency, and board member of the
Biopharmaceutical Section, the Danish Pharmaceutical
Society. He is also a member of the Danish Pharmacopoeia
Commission and its subcommittee on pharmacy, and the
Drug Registration Committee under the Danish Medicine
Agency. He serves as member of the editorial board for
Pharmaceutical Research and STP Pharma Sciences and he
is section editor on European Journal of Pharmaceutical
Sciences
Mette Rasmussen is chairman of the Section of Clinical
Pharmacy, The Pharmaceutical Society of Denmark.
Lona Christrup is chairman of the Danish Pain Society
Margrethe Rømer Rassing has been pharmaceutical editor
of the Danish Drug Catalogue (Lægemiddelkataloget) until
September 1 2001.
DONATIONS AND GRANTS
Jette Jacobsen has received DKK 10.000 from
Generalkonsul Ludvig Tegner og Hustrus Mindelegat for
analytical equipment.
Hanne Mørck Nielsen has received a grant from the Alfred
Benzon Foundation for a post doctoral stay at ETH Zürich,
Switzerland.
Heidi Ugelstad Eirheim has received DKK 8.000 from Kong
Chr. X´s Fond for analytical equipment.
Sven Frøkjær is centre director of a four-year grant “Centre
for Drug Design and Transport” (1997-2001) from the Danish
Medical Research Council, in total DKK 32,000,000. In
2001, DKK 770,000 is used for research on pharmaceutical
formulation of slightly soluble drugs and DKK 1,500,000 for
research on membrane transport and drug delivery systems.
The Alfred Benzon Foundation has granted Sven Frøkjær
DKK 445,000 to an Investigator Fellowship for Dr. Marco van
de Weert, Utrecht University.
Furthermore, Sven Frøkjær obtained DKK 200,000 form the
Alfred Benzon Foundation, DKK 200,000 from Novo
Nordisk A/S, DKK 50,000 from Pharmexa A/S, DKK120,000
from Lica Pharmaceutical A/S and DKK 392,000 from
“Apotekerfonden af 1991”. He has also obtained funding for
a PhD student from Øresundskonsortiet “Explorative Drug
Formulations” partly supported by Erhvervsfremmestyrelsen
and Vinnova from Sweden.
Birger Brodin was donated DDK 110.000 from The
Carlsberg Foundation to partly finance research chemicals.
Bente Steffansen was donated DDK 458.000 from Leo
Pharmaceuticals A/S to partly finance a PhD program.
Bente Steffansen was donated DDK 112.000 from Zealand
Pharmaceuticals A/S to finance the salary to a research as-
sistant.
Bente Steffansen was donated DDK 500.000 from The
Danish Research Academy to the project “Application of the
human intestinal peptide transporter as an absorption promo-
tor for compounds with poor bioavailability”.
Anne Engelbrecht Thomsen was donated DDK 6,300 for trav-
elling expenses from Knud Højgaards foundation.
Anne Engelbrecht Thomsen was donated DDK 6,400 for trav-
elling expenses from the Study Foundation The Danish
Pharmacy Union.
Birger Brodin and Carsten Uhd Nielsen were donated by DDK
7,000 for travelling expenses from The Scandinavian
Physiology Society Foundation.
PROJECTS
PHARMACEUTICAL FORMULATION/PROCESSING
TECHNOLOGY
Design of oral formulations by pelletization techniques
High shear mixers and a conventional as well as a rotary flu-
idised bed are applied for pelletization of powders.
Hydrophilic and hydrophobic meltable binders and aqueous
binder solutions are applied as binder liquids. The effects of
the physical and physicochemical properties of raw materials
and binders and the effects of process variables on the prop-
erties of the final pellets, e.g. porosity, disintegration and dis-
DEPARTMENT OF PHARMACEUTICS
PAGE 73
solution, are investigated. These studies are the basis of the
design of pellets with a modified drug release including pro-
longed release formulations, gastro-resistant formulations,
and colon specific delivery systems as well as pellets contain-
ing solid dispersions.
(Torben Schæfer, Helle Eliasen, Anita Johansen, Jakob
Kristensen, Anette Seo, Ole Wørts, Henning Gjelstrup
Kristensen, Per Holm, H. Lundbeck A/S, and Peter
Kleinebudde, University of Halle).
Absorption enhancing solid dosage forms
Different formulation principles and production techniques
that might be applicable for enhancing the oral absorption of
low soluble drugs have been screened. At the present time,
the preparation of dry emulsions by means of spray drying is
investigated. Different drug substances will be included in the
formulations, and the physical stability and the oral bioavail-
ability of the formulations will be tested.
(Tue Hansen, Per Holm, Kirsten Schultz, H. Lundbeck A/S,
and Torben Schæfer).
Microencapsulation by atomization techniques
The aim of the project is the encapsulation of solid particles
with polymers in order to modify and control the dissolution
rate of the solid. The project has, so far, dealt with the atom-
ization of polymer solutions using an effervescent atomizer.
The design of the atomizer has been optimized for spray dry-
ing processes. The studies shows that effervescent atomiza-
tion has some advantages compared to other atomization
methods: Reduced air comsumption, atomization of viscous
liquids and the possibility to produce small droplets.
(Frederik Pedersen, Torben Schæfer, Ole Wørts, Henning
Gjelstrup Kristensen)
Inhalable particles
The use of spray drying technology for the preparation of in-
halable particles is investigated in a project performed in a
collaboration with Lunds University and AstraZeneca R&D
Lund. The purpose of the project is to investigate and opti-
mise the physical stability of spray dryed powders with parti-
cle sizes in the range below 5 �m. Based on an investigation
on a series of carbohydrates it has been demonstrated that
the glass transitions temperature of the amorphous carbohy-
drate affects the crystallinity of the spray dried products. The
current studies focuses upon the possibilities to control the
crystallinity of spray dried particles.
(Kristina Ståhl, Anders Axelsson, Lunds University, Kjell
Bäckström, AstraZeneca R&D Lund, Torben Schæfer and
Henning G. Kristensen)
Formulation of nebuliser liquids
The aim of the project is to formulate solutions of antibiotics,
which are deliverable to the airways and lungs for the treat-
ment of infections by fungi. So far, the project has been con-
cerned about the development of an in vitro model to simu-
late the deposition of the antibiotic in the airways. Various
nebulisers are investigated. The model will be used to evalu-
ate formulated solutions and suspensions.
(Kenneth Manby Pedersen, Vagn Handlos and Lars Heslet,
State University Hospital)
Evaluation of the compression and
compaction characteristics of powders
The project includes a critical evaluation of the Heckel and
Walker equations and their ability to describe the compress-
ibility of powders. A model for description of compactibility
(the ability of a powder to cohere into or to form a compact)
and the lamination tendency is investigated through combina-
tion of the elastic properties under pressure and the Walker
coefficients of plastic deformation. The statistical distribution
of crushing strength of tablets has been investigated and
confirmed the hypothesis that the data followed a standard
normal distribution rather than the general accepted Weibull
distribution.
(Jørn Møller-Sonnergaard, Henning Gjelstrup Kristensen)
Critical compaction characteristics of pellets
and excipients with impact on the physical stability
of polymer membranes.
The release of drug from Modified-release tablets formulated
with filmcoated pellets (polydepot) are controlled by the poly-
mer membrane. By compaction of the pellets the membrane
will be damaged or distorted with a uncontrolled effect on the
dissolution rate of the tablet. The aim of the project is to in-
vestigate the combination of pellet manufacturing method,
type of polymer film and tablet excipients that minimizes the
negative effect on the dissolution rate.
(Casper Crilles Larsen, Per Holm, H.Lundbeck A/S, Jørn
Møller-Sonnergaard)
Gastrointestinal solubility of low soluble drugs (GISOL)
The GISOL-projects focus upon the in vivo and in vitro disso-
lution of low soluble drugs belonging to Class II in the
Biopharmaceutics Classification System. The research group
has established predicative dissolution methods based on
media simulating the composition of the gastrointestinal fluids
in fasted and fed states. Further, an in vitro lipolysis model
has been developed for studies of the dissolution of hy-
drophobic drug substances, e.g. danazol and probucol. The
use of the model is being investigated by studies on a range
of drug substances characterised by log P values in the
ANNUAL REPORT 2000–2001
PAGE 74
range of 3 – 10; these studies are performed in collaboration
with H. Lundbeck A/S, Denmark, and Aventis Pharma, Germany.
The possibility for establishing in vivo in vitro correlations by
the use of the simulated media for dissolution testing is inves-
tigated in a study on the absorption of danazol. The effects of
meals and fluid intake are subject for a clinical study, which in
a later stage will be compared with dissolution data in order
to elucidate for example effects of the in vivo hydrodynamics.
In 2001 a new project on in vivo in vitro correlations of lipid-
based oral formulations, e.g. microemulsions and SEDDS,
has been established in the Øresund region. External partners
participating in the project are Lunds University, AstraZeneca
Lund, Cumurus, Lund, Nycomed Pharma, Denmark, DTC
Denmark and Scantox Denmark.
Other ongoing research projects concern the transport of
solubilised drug substances across Caco2 cell monolayers
and the evaluation of the micellar properties of dissolution
media simulating the jejunal fluids.
(Niels Hønberg Zangenberg, David Ilardia, Vikeke Hovgaard
Sunesen,Flemming Seir Nielsen, Anette Müllertz, Lars
Hovgaard and Henning G.Kristensen)
Lipid-based formulations for oral
delivery of low soluble drugs
Lipid-based formulations for oral delivery utilise the degrada-
tion pathways of triglycerides and other lipids to improve the
dissolution and absorption of hydrophobic drug substances.
A project on the use of tocopherols as a vehicle for low solu-
bile drugs has been concluded in 2001. The influence of
lipids upon the lymphatic transport of drug substances has
been the object for studies in the past three years, partly in
collaboration with Professor W.N. Charman, Australia. Animal
models (rats, dogs) has been established for investigating the
effects of various triglycerides on the lymphatic transport and
systemic absorption of halophantrine. In the continuation of
the project attention is paid to the pharmacokinetcs and lym-
phatically transported drug substances. Another project con-
cerns formulation and evaluation microemulsions for oral de-
livery of drugs. This project is performed in a collaboration
with H. Lundbeck A/S Denmark.
(René Holm, Janne Ørskov Christensen, Pernille Bondeskov
Nielsen, Ditte Maria Karf, Tomas Norling, Dumex-Alpharma,
Kirsten Schultz and Birgitte Mølgaard, H. Lundbeck A/S,
Betty Lomstein Pedersen, Nycomed Pharma, Anette Müllertz
and Henning G. Kristensen).
Solid lipid nanospheres
The potential use of SLN technology to reduce of the aquatic
toxicity of pesticides is investigated in a project performed in
a collaboration with Cheminova A/S. The physical stability of
SLN based on two types of lipophilic carriers is affected by
the formulation, in particular by the compatibility of the active
substance and the lipid and by the choice of surfactant. A
stable SLN system has been developed and submitted to
various tests on insects and fish.
(Henrik F. Frederiksen, Morten Pedersen, Anita Wengel and
Henning G. Kristensen)
Particulate formulation of DNA-vaccines
or protein-based vaccines
Pharmaceutical formulation of nanopheres based on lipids to
be loaded with
DNA is the subject for a collaborative research with the
State University Hospital, Copenhagen, and Statens
Seruminstitute. The research aims at a formulation intended
for mucosal application. In another project performed in a col-
laboration with Pharmexa, Denmark, the aim is to develop a
particulate vaccine formulation based on a polymeric carrier.
(Annette Vinther Heydenreich, Anne Mette Beyer, Regina
Westmeyer, Lars Hovgaard, Henning G. Kristensen, Annan
Gautam, Pharmexa, Hans Skovgaard, the State University
Hospital)
PHARMACEUTICAL FORMULATION/DRUG DELIVERY
Parenteral depot formulations
Until now, the most successful principle to control drug re-
lease from oily depot formulations have been by modifying
the partition coefficient of the drug substance, e.g. by using
prodrugs. There have been less interest in developing more
general formulation principles. In the present project, water-
in-oil emulsions are studied as potential depot formulations
for water-soluble drug substances including proteins.
(Simon Bjerregaard Jensen, Lene Jørgensen, Charlotte
Vermehren and Sven Frøkjær )
Pharmaceutical characterisation of chalcones
A number of chalcones have been shown to be effective as
antiparasitic compounds. However, this class of compounds
posseses physico-chemical properties which make the phar-
maceutical formulation challenging. Based on results from
preformulation studies, various lipid based formulations are
developed in order to optimise the therapeutic effect of se-
lected chalcones.
(Sven Frøkjær, Bente Steffansen, Agnete Dyssegaard and
Søren Brøgger Christensen, Department of Medicinal
Chemistry and Arsalan Kharazmi, Department of Clinical
Microbiology, The State University Hospital/Lica
Pharmaceutical A/S).
Protein stability
Denaturation, aggregation, and precipitation of proteins are
major problems in the formulation of protein based drugs. A
DEPARTMENT OF PHARMACEUTICS
PAGE 75
Undergraduate
Researcher Agnete
Dyssegaard by the
apparatus.
more basic understanding of the molecular mechanisms for
protein fibrillation and the factors, which have an influence on
the fibrillation, may serve as a model for other globular pro-
teins and, thereby, improve the rational for developing pro-
tein-based drug in general. The kinetic of insulin fibrillation
and the effects of excipients on conformation and conforma-
tional changes on the stability of therapeutically relevant pro-
teins is studied. Other aspects of protein stability, which are
investigated, relates to the understanding of interfacial effects
on the physical stability of proteins in pharmaceutical sys-
tems.
(Liza Nielsen, Susanne Sønderkær, Susanne Møllmann,
Marco van de Weert, Sven Frøkjær, Ejvind Jensen and Peter
Langballe, Novo Nordisk A/S, Lars Lindgaard Hansen,
Pharmexa A/S, Jens Brange, Brange Consult, Ulla Elofsson,
Swedish Institut of Surface Chemistry, and John Carpenter,
University of Colorado).
Transdermal patches
The objective of project is to study the release kinetics of en-
hancers and drug substances from transdermal patches and
to study how the enhancer effect on various drug substances
is dependent on the release kinetics of the enhancer. The in-
fluence of enhancer on characteristics of importance for the
application of patches, e.g. adhesive properties, is also stud-
ied. This project is completed by December 2001.
(Michael H. Qvist, Sven Frøkjær, Flemming Madsen, Coloplast
A/S, Bo Kreilgård, Leo Pharmaceutical Products A/S and Ulla
Hoeck, Pharmacia & Upjohn)
Carrier mediated transport
Many different factors may influence on drug/prodrug absorp-
tion after oral administration. One of the main barriers for oral
drug absorption may be that many compounds display poor
permeability across biological membranes. Factors such as
the physico-chemical property of the compound, its in vitro
metabolism as well as efflux and influx transport
mechanism(s) may influence on its netto transepithelial trans-
port.
The main objective of the project is to investigate the im-
portance of carrier-mediated transport of selected com-
pounds including prodrugs, especially hPepT1-mediated
transport.
The strategies for the project are that the compounds in
question are characterized by investigating their pKa’-value(s),
aqueous stability, in vitro metabolism, affinity for hPepT1 as
well as their transepitheale transport. Structure-affinity-relation
(SAR) as well as other relations such as structure-hydrolysis
relations for various ester (model) prodrugs is an integrated
part of the project.
Pseudo-3-D image of a Caco-2 cells. Caco-2 cells grown for three weeks
in culture on permeable filters forms monolayers, which can be visualised
by confocal laser scanning microscopy. Image details: Nuclei are labelled
with propidium iodide (red) and the actin skeleton of the cells is labelled
with Alexa-488 phalloidin (green). The image was generated on a Zeiss
LSM 510 by Birger Brodin
ANNUAL REPORT 2000–2001
PAGE 76
DEPARTMENT OF PHARMACEUTICS
PAGE 77
A confocal laser scanning image of Caco-2 cells. The caco-2 cell line is a
commonly used cell model of the small intestinal epithelium, and express
the peptide transporter hPepT1 at the apical membrane. Image details:
Nuclei are labelled with propidium iodide (red) and the actin skeleton of
the cells is labelled with Alexa-488 phalloidin (green). The image was gen-
erated on a Zeiss LSM 510 by Birgitte Eltong/Susanne N Sørensen.
partition coefficient of the drug substance, e.g. by using pro-
drugs. There have been less interest in developing more gen-
eral formulation principles. In the present project, water-in-oil
emulsions are studied as potential depot formulations for wa-
ter soluble drug substances including peptides and proteins.
(Lene Jørgensen, Charlotte Vermehren, Sven Frøkjær and
Simon B. Jensen, Novo Nordisk A/S).
Liposomes as drug delivery system against inflammation
The project focuses on development of a specific delivery
system which carries the drug to inflammatory tissue.
Transport and release of drug may potentially be controlled by
utilizing the local conditions of the target organ, e.g. specific
enzyme activities. The phospholipid degradating enzyme,
phospholipase A2, exists in increased concentration in inflam-
matory tissue.
The degradation of long-circulating, surface modified lipo-
somes by phospholipase A2 is faster compared to conven-
tional phospholipid liposomes. Studies of the fate of surface
modified liposomes in infected tissue in rats in vivo are included
in the project as well.
The project includes studies of activity of inflammatory exu-
date containing liposome degradating factors, e.g. phospholi-
pase A2 and macrophages, toward surface modified lipo-
somes.
(Charlotte Vermehren, Sven Frokjaer, Jesper Davidsen in col-
laboration with Kent Jørgensen, Liplasome A/S and professor
Gert Storm, Department of Pharmaceutics, Utrecht Institute
for Pharmaceutical Sciences, Utrecht, The Netherlands).
Surface properties of lipid membranes
and the association of small acylated peptides
Acylated peptides and proteins can bind to surfaces of lipid
membranes by electrostatic and hydrophobic forces. Acylated
peptides and proteins display an increased circulation time in
the blood stream – which from a drug delivery perspective
make them interesting. The aim of the project is on the one
hand to investigate how the membrane association of acylated
peptides affects the lipid membrane behavior and on the other
hand how the membrane association affects the secondary
structure of the peptide.
(Tina Bjeldskov Pedersen, Sven Frøkjær, Kent Jørgensen and
Ole G. Mouritsen in collaboration with The MemPhys group,
Department of Chemistry, Danish University of Technology).
Activity of membrane associated enzymes in relation to
surface modified liposomes
Incorporation of different amounts of lipopolymers into lipo-
somes increases the in vitro and in vivo stability. This is mani-
fested as a significant prolongation of the intravascular circu-
lation time. The project involves studies of the activity of lipo-
some degrading enzymes such as phospholipase A2 and C
To improve the understanding of carrier mediated drug de-
livery certain regulatory aspects are investigated. Regulation
of hPepT-1 is a highly integrated part of the project since cer-
tain growth factors/hormones influence on expression and
transport activity of hPepT1.
Also substrate-induced regulation of hPepT1 transport
activity is investigated.
Prodrug design and SAR-analysis are primarily performed in
cooperation with Department of Medicinal Chemistry, how-
ever Leo Pharmaceuticals A/S and Zealand Pharmaceuticals
A/S are also involved to a limited degree.
(Rikke Andersen, Carsten Uhd Nielsen, Anne Engelbrecht
Thomsen, Camilla Foged, Birger Brodin, Bente Steffansen,
Andre Huss Eriksson, Thomas Andersen, and Sven Frøkjær.
In collaboration with: Mikael Begtrup, Peter Elm, Flemming
Jørgensen Department of Medicinal Chemistry; Jan Amdrup,
August Krogh Institute, University of Copenhagen; Hans
Lennernäs, University of Uppsala, Sweden; Frederik Björklin,
Leo Pharmaceuticals A/S, Denmark; Bjarne Due Larsen,
Zealand Pharmaceuticals A/S, Denmark; Mitchell E. Taub,
Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA.)
Parenteral depot formulations
Until now, the most successful principle to control drug re-
lease from oily depot formulations has been by modifying the
towards surface modified liposomes. Such results are of im-
portance for a deeper understanding of the mechanisms in-
volved in the extravascular stabilization and release of incap-
sulated material from the liposomes.
(Jesper Davidsen, Charlotte Vermehren, Sven Frøkjær, in col-
laboration with Kent Jørgensen, Liplasome A/S and Ole G.
Mouritsen, The MemPhys group, Department of Chemistry,
Danish University of Technology).
NAPE-containing liposomes
Incorporation of the phospho-
lipids N-acyl-phosphatidyl-
ethanolamines (NAPE) into li-
posomes stabilizes the lipo-
somes in the presence of hu-
man serum. The stabilization
of NAPE-containing liposomes
in serum may be attributed to
different factors such as
changes in fluidity and vesicle
surface. The project focuses
on the in vivo behaviour of li-
posomes containing different
amounts of NAPE as well as
the destabilization of these li-
posomes by enzymatic degra-
dation and lipid exchange.
(Charlotte Vermehren, Sven
Frøkjær in collaboration with
Harald S. Hansen and Gitte
Petersen, Department of
Pharmacology).
Transport across
biomembranes
The objective of this project is to obtain a more basic under-
standing of key parameters of importance for passive diffu-
sion of drug substances across biological membranes. This
may contribute to the development of in vitro characterisation
programs with a greater predictive power than the methods
used to day. Presently, peptides and peptide analogs are
used as model compounds. This makes it possible to study
the importance of molecular parameters such as conforma-
tion, molecular weight, lipid-water partitioning water accessi-
ble surface, and surface polarity. The influence of absorption
enhancers on membrane transport of drug molecules is also
studied in various models.
(Lene Krarup, Jan Høst, Lars Hovgaard, Sven Frøkjær in col-
laboration with Flemming Steen Jørgensen, Department of
Medicinal Chemistry and Inge Thøger Christensen, Novo
Nordisk A/S)
Intranasal application of drugs e.g. peptides
The research is primarily concentrated on studying the poten-
tial of intranasal administration. The focus is especially on
drugs used in acute situations and delivery of peptide drugs.
The various projects include the study of in vitro/vivo perme-
ation, degradation of drugs and estimation of low irritating
potential absorption enhancers. The absorption and distribu-
tion into the brain after nasal application is also an issue.
(Erik Bechgaard, Morten Bagger, Karsten Lindhardt in collab-
oration with Sveinbjørn Gizurarson, University of Iceland)
Solubilisation of low solubility drugs
for intranasal application
The maximum volume for nasal application is normally 50-100
�l per nostril. Therefore, it is often necessary to use cosol-
vents in nasal formulations to be able to dissolve a clinical
dose. Cosolvents, however, may give rise to local mucosal ir-
ritation, why it is important to identify substances and con-
centrations, which are effective and at the same time accept-
able in relation to the indication. Various formulation aspects
are evaluated for low solubility drugs and the bioavailability
from formulations is studied in rabbits and sheep, providing
the possibility of correlating the two animal models.
(Erik Bechgaard, Karsten Lindhardt in collaboration with
Sveinbjørn Gizurarson, University of Iceland)
ANNUAL REPORT 2000–2001
PAGE 78
Intranasal administration.
Intracerebral microdialysis: Probe implantation procedure per-
formed on an anaesthetised rat
Olfactory absorption
Distribution of drugs to the brain following nasal ad-
ministration
Intracerebral microdialysis in the rat has been imple-
mented as a model for studies of olfactory absorp-
tion of drugs. The model has been characterised in
terms of blood-brain barrier integrity following probe
implantation. The model has been found to be suit-
able for determinations of unbound concentrations
of drugs in vivo in the extracellular fluid of blood and
brain, based on dialysate concentrations.
Specifically, pharmacokinetic studies of drug ab-
sorption and distribution to blood and brain follow-
ing unilateral nasal administration to rats, has been
carried out using lidocaine, fluorescein and mor-
phine-6-glucuronide as model substances.
Experiments with morphine-6-glucuronide were performed as
a pilot study. With lidocaine, which easily passes the blood-
brain barrier, no signs of olfactory absorption were found, nei-
ther as higher extracellular concentrations in the brain nor as
higher absorption rates following nasal administration. With
fluorescein, which has a low blood-brain barrier permeability,
the study showed higher absorption rates and lower Tmax
values in the right side of the brain following unilateral nasal
administration indicating limited olfactory absorption in the
rat.
(Erik Bechgaard and Morten Bagger)
In vitro models for buccal mucosa
In vitro models for buccal mucosa have been employed to
study buccal permeability and toxicity of drugs, including
peptides, and pharmaceutical adjuvants.
One model is based on the cell line TR146 originating from
a human buccal carcinoma. Filter-grown TR146 cells form a
multilayered epithelium and studies of morphology, perme-
ability and profile of keratins have demonstrated a differentia-
tion pattern of TR146 cells similar to normal human buccal
epithelium. Another model is based on porcine and human
buccal mucosa mounted in the Ussing chamber. Characteris-
tics of the in vitro models have been evaluated, e.g. compari-
son of enzyme activities and the influence of molecular size
and lipophilicity on the permeability of drugs as well as the ef-
fect of bile salt enhancers. The effect of pH on the permeabili-
ty of drugs, e.g. nicotine, has been investigated.
(Jette Jacobsen, Hanne Mørck Nielsen, Margrethe Rømer
Rassing)
Toxicity assessment in the TR146 cell culture model –
development, optimization and comparison of assays
Different toxicity assays has been optimized for dividing
TR146 cells and for TR146 epithelium for three different per-
meability enhancers in order to investigate the mechanisms
of action.
(Heidi Ugelstad Eirheim, Hanne Mørck Nielsen)
Iontophoresis as a technique to enhance
in vitro buccal drug delivery
Iontophoresis as non-invasive physical enhancer in buccal
drug delivery has been studied. The results demonstrated the
feasibility of the iontophoretic approach to enhance and con-
trol the rate of buccal drug delivery. A new three-chamber
iontophoretic diffusion cell has been developed to reflect the
in vivo iontophoretic drug delivery more closely.
(Jette Jacobsen, Margrethe Rømer Rassing)
Epidermal growth factor (EGF): in vitro and in vivo
studies and clinical testing of treatment of oral
mucositis induced by radiotherapy
The overall objective of the project is the introduction of a
new medical therapy with topical application of EGF in cancer
patients to relief oral mucositis induced by radiotherapy. The
project includes studies on EGF on the cell line TR146, devel-
opment of a pharmaceutical formulation with EGF, studies of
the healing effect of EGF on oral mucositis and clinical testing
of the pharmaceutical formulation. Initial studies have been
carried out.
(Hanne Mørck Nielsen, Margrethe Rømer Rassing in collabora-
tion with Helle Birgitte Dahl Olin, Maria Elisabeth Christensen,
State University Hospital)
DEPARTMENT OF PHARMACEUTICS
PAGE 79
Intercellular matrix in the TR146 cell culture model and in
vivo/in vitro correlation to human buccal epithelium.
The objective of the project is to characterize the lipid content
of the intercellular matrix in the TR146 cell culture model and
to examine the influence of different enhancers on the lipid
structure. Furthermore, to correlate the permeability of drug
substances across the TR146 cell culture model to the per-
meability across human buccal mucosa in situ. For the in vivo
studies a custom-designed chamber has been developed.
Nicotine has been chosen as a first model substance.
(Charlotte Adrian, Margrethe Rømer Rassing in collaboration
with Helle Birgitte Dahl Olin, State University Hospital)
CLINICAL PHARMACY
Development and maintenance of a quality assurance system
for the medication procedures in a critical care unit.
The aim of the project is to reduce the number of medica-
tion errors and to improve drug therapy.
(Lona Christrup, Mette Rasmussen in collaboration with
Intensive Care Unit, Herlev University Hospital ).
Long-term treatment of chronic pain patients with morphine
The aim of the study is to gain knowledge of the connection
between dose/administration route, plasma concentration of
morphine/morphine metabolites and side-effects and analge-
sia, in order to improve the treatment of patients suffering
from chronic pain.
(Lona Christrup, Steen Honoré Hansen, Department of
Analytical and Pharmaceutical Chemistry, in collaboration with
the Multidisciplinary Pain Centre, Herlev University Hospital).
Local ocular pain treatment with opioids
The aim of the project is to evaluate if opioids applied locally
in the eye can exert analgesia if it is mediated by peripheral
opioid receptors. The transport of opioids across the cornea
and the distribution in the eye are investigated in vitro and in
vivo in rabbits. Additionally, the analgesia following adminis-
tration of opioids in the eye in a clinical set up is investigated.
(Lona Christrup, Bente Steffansen in collaboration with
Department of Pharmacology, The Royal Veterinary and
Agricultural University, The Pain Clinic, Aalborg University
Hospital, and the Multidisciplinary Pain Centre, Herlev
University Hospital).
LAAM - potential use as an opioid analgesic
LAAM is an opioid drug, and when used in the maintenance
treatment of drug addicts to suppress abstinence syndroms,
it has a duration of action of 3-4 days. The purpose of the
study is to evaluate if LAAM has a future as an analgesic drug
substance. The binding of LAAM and its two metabolites nor-
and dinor-LAAM to the opioid and NMDA receptors is investi-
gated in vitro. The analgesic effect of all three substances is
evaluted after administration in mice. The duration of action
with respect to analgesia as well as the equipotential doses
to methadone is investigated in patients suffering from chron-
ic pain. Finally, a HPLC method for quantification of LAAM
and its metabolites is being set up.
(Lona Christrup, in collaboration with H:S Multidisciplinary
Pain Centre, Copenhagen University Hospital and Department
of Clinical Biochemistry, Bispebjerg University Hospital).
Pharmacokinetics and -dynamics of paracetamol
The pharmacokinetic and -dynamic parameters of paraceta-
mol are investigated in adult postoperative patients in order to
optimize pain management with paracetamol.
The pharmacokinetics of paracetamol are also investigated
in the postoperative phase in children.
Oral, intravenous and rectal administration is used.
(Mette Rasmussen and Janne Rømsing in collaboration with
physicians at hospitals in Copenhagen, and Tina Hahn,
Coloplast A/S)
Non-opioid analgesics
To improve postoperative pain management in ambulatory
surgery patients, several projects are carried out evaluating
the analgesic effect of non-opioid analgesics. The research
focuses on mechanism of action, pharmacokinetics and -dy-
namics, and side effects of the drugs. The use of a multi-
modal approach as well as the influence of different formula-
tions of the drugs on analgesia are investigated.
(Janne Rømsing, Tina Hoff Duedahl in collaboration with
physicians at Herlev and Gentofte University Hospitals and at
the State University Hospital).
Pharmacokinetics of prednisolone.
The prognosis for children with acute lymphoblastic leukemia
depends on the amount of residual disease after four weeks
of treatment. In this project, a possible correlation between
the plasma concentration of prednisolone and the amount of
residual disease is evaluated. Further, the kinetics of pred-
nisone is examined and the bioavailability is evaluated in rela-
tion to the gastro-intestinal function. Oral and intravenous ad-
ministration is used.
(Kamilla B. Petersen and Mette Rasmussen in collaboration
with physicians at The National University Hospital,
Rigshospitalet).
ANNUAL REPORT 2000–2001
PAGE 80
DEPARTMENT OF PHARMACEUTICS
PAGE 81
Department ofPharmacology
The Department of Pharmacology conducts research and
teaching within a broad biological field including biochemistry,
microbiology, physiology, pharmacology, pharmacotherapy
and molecular biology focusing on effects and side effects of
drugs and their importance in connection with pathological
conditions.
A detailed broad spectrum of knowledge about drug effects
and the methods used to investigate them at cellular levels, in
isolated tissues, in the whole animal and in patients, is of fun-
damental importance and an indispensable basis for drug ex-
perts. The teaching gives pharmacists in-depth knowledge
about biochemistry and microbiology, including molecular bi-
ology and integrated pharmacological knowledge in which
anatomy, physiology, pharmacology and biological standard-
ization are integrated. This knowledge will enable pharmacists
ANNUAL REPORT 2000–2001
Head of Department: Associate Professor Erik Wind Hansen, PhD
PAGE 82
to function as drug experts. The research at the Department
forms the scientific basis for the education.
RESEARCH
Research at the Department of Pharmacology covers a wide
range of activities directed at drugs, their effects and side ef-
fects, their importance in connection with pathological condi-
tions, as well as their effects on the immunological system.
Research includes biochemical, pharmacological, pharma-
cokinetic and molecular biological studies related to charac-
terisation and development of specific drugs. It is based on
studies in cell cultures, isolated tissues and smaller animals
and includes, among other thing, characterisation of recep-
tors, transport systems in cell membranes, mechanisms for
regulation of biosynthesis and for release of peptides, studies
of second messengers, intracellular mechanisms and various
gene techniques. Primary research fields are pharmacology
(including neuro-, molecular- and vascular pharmacology),
molecular biology and pharmaceutical microbiology.
Pharmacological research aims to improve the clinical use
of drugs. Current research in the vascular pharmacological
area focuses on the transduction mechanisms for peptides
and classical neurotransmitters in cerebral, ocular and coronal
vascular tissues from animal and humans in relation to dis-
eases like migraine, ischæmia and diabetes. Neuropathic pain
is a new research field at the Department. A set of rat models
for neuropathic pain is under establishment for testing with
new and well-known antagonists and agonists for the in-
volved receptor systems. The goal of the project is to improve
the treatment of neuropathic pain.
The molecular- and neuropharmacological research seeks
to improve understanding of the effects of neuro-active amino
acids, an important part of the efforts to develop new drugs
to treat neurodegenerative diseases. The research is interdis-
ciplinary in its combination of molecular, cellular and pharma-
cological aspects of neurotransmitters. Current research fo-
cuses on GABA as a neurotransmitter, on glutamate- and
GABA-mediated neurotransmission, on the formation of en-
docannabinoids and on opioid- and NMDA-receptors using
cell cultures, isolated tissues and electrophysiological tech-
niques. The molecular and cellular role of different mediators
e.g. cytokines and nitrogen oxide in neurotoxic and neuropro-
tective effects in the brain is another issue in neuropharmaco-
logical research. Communication between the neuroendocrine
and the immune system in the neurohypophysis is another
area of study. Other research objects are the biological func-
tion of essential fatty acids and phospholipases in the cell
membrane, receptor mediated regulation of intercellular en-
zymes and the formation of second messengers.
The molecular biology group uses genetic engineering to
generate novel antibodies and peptides relevant to the diag-
nosis and treatment of immunological diseases. Current re-
search focuses on generating recombinant antibodies with
antigen-specific MHC restricted specificity of T cells used as
reagents for basic and clinical investigations and immunother-
apy. The detailed involvement of selected viral surface pro-
teins in viral infection cycle is another area of investigation.
Pharmaceutical microbiological research focuses on the de-
velopment of new methods to evaluate pharmaceuticals.
Current research concerns in vitro pyrogen testing based on
the use of cell lines.
TEACHING
The Department teaches compulsory theoretical courses in
biochemistry, physiology and biological standardisation, mi-
crobiology, anatomy, pharmacology and pharmacotherapy to-
gether with laboratory courses in microbiology and pharma-
cology. In the period under review, the Department taught
elective courses in pharmacokinetics and pharmacodyna-
mics, basic methods in molecular biology, experimental phar-
macology in-vitro, biochemical laboratory technique, micro-
biological and immunological methods of drug control.
The work to make a radical change in teaching in order to
focus on pharmacology continues. The new curriculum will
come into force starting next term, which means that courses
in anatomy, physiology and biological standardisation and
pharmacology will be integrated into two courses: basic phar-
macology and organ-related pharmacology. The Department
of Pharmacology together with the Department of Pharmacy
DEPARTMENT OF PHARMACOLOGY
PAGE 83
also held a compulsory course in pharmacotherapy. Finally,
an introductory course in cell biology was introduced.
About 40 students have completed their master’s theses in
connection with the Department; half of these students re-
ceived their practical training in foreign research laboratories
(pharmaceutical industry and abroad).
Some staff members were involved in PhD courses both at
the School and at other universities again this year.
MEMBERSHIP OF EXTERNAL COUNCILS AND BOARDS
Klaus Bahl Andersen is censor of Aarhus University,
December 2001.
Ole J. Bjerrum is Adjunct Professor of Centre for Proteome
Analysis, University of Southern Denmark. Fellow, Danish
Academy of Natural Sciences. Fellow, Danish Academy of
Technical Sciences. Danish delegate: EU 5th Framework
Programme Management Committee on Quality of Life.
Member of Governing board, European Association for pro-
motion of Science & Technology (EUROSCIENCE). Member of
Faculty, European Centre for Pharmaceutical Medicine
(ECPM). Appointed member, Advisory Research Council,
Ministry of Health. Appointed member, Advisory group for EU
5th Framework programme for Quality of Life and Mobility
and Training, IT and Research Ministry. Appointed member,
Advisory board Danish Technology Council. Member of
Scientific Committee for EUFEPS Conference on Optimizing
Drug Development: “Use of Biomarkers: From Drug Discovery
through Clinical Practice”, Basel, December 2001. Chairman
for EUFEPS Conference on Optimizing Biotech Medicine:
“Rational Development of Therapeutic Proteins”, Berlin, May
2002. Member of Organizing Committee Eufeps Congress:
“EUFEPS 2002. New Safe Medicine Faster”, Stockholm,
October 2002. Organizer of Course of Industrial Drug Deve-
lopment for Danish Pharma industry and Danish School of
Pharmacy.
Jan Engberg is member of the reviewing boards of: Immuno-
technology, Biochim. Biophys. Acta, Journal of Immunological
Methods, Nucl. Acids Res, Trends of Biochemical Sciences,
Biotechnology, FEBS-letters and Proceedings of the National
Academy of Science (USA). He is member of the advisory
boards of the National Research Councils for medical scien-
ces in Holland, Sweden and Australia and member of evalua-
tion committees at the faculties of Medical and Natural Scien-
ces in Copenhagen, Aarhus, Odense and Roskilde.
Bjarne Fjalland is member of the reviewing board of: Eur. J.
Pharmacol., Eur. J. Physiol., J. Neuros. Res., Psychopharma-
cology and Pharmacology & Toxicology.
Aase Frandsen is President of the Danish Society for
Neuroscience and member of the council for The National
Association for Treatment of Brain Disease. She is member of
the council for The Federation of European Neuroscience
Societies (FENS) and member of the governing council for
International Brain Research Organisation (IBRO). Organizer
of meeting of EU consortium ERDYS. Editor of Journal of
Neurochemistry. Referee for Journal of Neurochemistry,
Neurochemistry International, Brain Research, Neuropharma-
cology, Journal of Cerebral Blood Flow and Metabolism,
European Journal of Biochemistry, Journal of Clinical Ana-
tomy, and Journal of Neuroscience Research. Officially ap-
pointed examiner at the University of Copenhagen.
Georgi Gegelashvili is member of the reviewing boards of
Neuroreport, J. Neurotrauma, Brain Research, FEBS Letters,
and J. Neurosci. He serves as a vice-chairman for the
Georgian NeuroForum and represents this society in the
European Glia Network.
Harald S. Hansen censor at DTU and KVL and has been in-
ternational reviewer for a grant application to Science Foun-
dation Ireland. He has been member of the assessment com-
mittees for PhD-theses at DFH, at Biocentrum-DTU and at
Syddansk University Odense and been chairman for the as-
sessment committee for a professorship at DFH. He is mem-
ber of the Board of directors for The Danish Nutrition Society,
for International Society for the Study of Fatty Acids and
Lipids (ISSFAL), is alternate member of The Danish Commit-
tees on Scientific Dishonesty, the Danish State Nutrition
Council, is member of 2 consulting groups affilated to the
Danish State Nutrition Council concerned with “Dietary fat,
children and atherosclerosis” and “Dietary prevention of obe-
sity”, and chairman for the National Council of Nutritional
Science at the Royal Danish Academy of Sciences and
Letters.
Inger Jansen Olesen is member of the Danish Pharmaco-
logical and Toxicological Society, the International Headache
Society, The International Society of Cerebral Blood Flow and
Metabolism. She is a member of the reviewing board of Br. J.
Pharmacol., Stroke and Cephalalgia.
Arne Schousboe is member of Editorial Board of: J. Neuro-
chem., Neurochem. Res., Neurochem. Int. (Assoc. Ed.), J.
Neurosci. Res. (Assoc. Ed.), Exp. Brain Res., Glia, Int. J. Devl.
Neurosci. (Assoc. Ed.), Devl. Neurosci. and Eur. J. Pharmacol.
He is external examiner at the Faculty of Health Sciences and
the Faculty of Science, University of Copenhagen. He is a
member of the Advisory Board of the National Science
Foundation (USA), Medical Research Council (UK), The
Wellcome Trust (UK) and Human Frontier Science Program
ANNUAL REPORT 2000–2001
PAGE 84
(France). He is registered in the ISI-Thomson list “Highly Cited
Researchers” of the 100 most frequently cited researchers in
the field Neuroscience (www.isihighlycited.com).
DONATIONS AND GRANTS
Tue Banke has received a post-doc scholarship from The
Alfred Benzon Foundation for a stay of one year at Dept.
Pharmacol., Emery Univ., Atlanta, Ge, USA and has received
a 3-year post-doc scholarship from The Danish Medical
Research Council (2002-2004).
Ole Jannik Bjerrum has received DKK 15.000 from Novo
Nordic, DKK 350.000 from EU Accompanying Measures:
EUFEPS 2002: New Safe Medicine Faster. An integrated
Congress.
Jan Engberg has received The following funding (for projects)
DKK 150.000 from The Danish Cancer Society “Generation
of recombinant antibodytoxins directed against tumor associ-
ated peptide/HLA complexes with T cell receptor-like speci-
ficity”, DKK 312.715 from The Novo Nordic Foundation
“Generation of recombinant antibodies specific for MHC/pep-
tide complexes of relevance for the pathogenesis of multiple
sclerosis”, DKK 89.660 from The Danish Research Council
for Medical Sciences. Identification of hippocampus specific
corticosteroid-specific genes using DNA micro arrays and
DKK 300.000 from Apotekerfoundation “Generation of re-
combinant antibodies specific for MHC/peptide complexes of
relevance for the pathogenesis of multiple sclerosis”.
Bjarne Fjalland has received DKK 200.000 from The Lund-
beck Foundation and DKK 100.000 from Ib Henriksen
Foundation in support of the project “CGRP - an important
partner in painperception”.
Aase Frandsen has received DKK 60.000 from SSVF Start
Program (22-01-0054).
Georgi Gegelashvili continued to administer research grants
received DKK 600.000 per year, for the period 1998-2002
from The Danish Medical Research Council, DKK 40.000
from The Novo Nordic Foundation. He has obtained further
funding DKK 88.350 from The Novo Nordisk Foundation for
the period 2001-2002, and DKK 260.000 from The Danish
Medical Research Council for year 2002. He has received a
senior visiting fellowship and a research grant from The Alfred
Benzon Foundation DKK 150.000 for a project carried out in
the USA 2000-2001. He has been awarded a Bøje Benzon
Stipendium DKK 520.000 per year.
Harald S. Hansen has received DKK 750.000 from SSVF,
DKK 280.000 from Carlsberg Foundation, DKK 400.000
from Lundbeck Foundation, DKK 300.000 from Augustinus
Foundation, DKK 50.000 from Director Ib Henriksens
Foundation, DKK 100.000 from Eva & Henry Krænkels
Memorial Foundation, DKK 90.000 from Novo Nordic
Foundation.
Arne Schousboe had a 3-year grant from The Lundbeck
Foundation (DKK 400.000 per year (1999-2001)). He has re-
ceived a 3-year grant from The Danish Medical Research
Council (2001-2004; DKK 500.000 per year).
Helle S. Waagepetersen has a 31/2-year (2000-2003) post-
doc grant (DKK 600.000 per year) from The Danish Medical
Research Council.
STAFF
In the past year Ole Jannik Bjerrum was appointed professor
of pharmacology and the position of associate professor in
pharmacology was reappointed. At the moment two positions
as associate professors in pharmacology are vacant due to
resignation. One position has been upgraded to a full profes-
sorship in pharmacokinetics and drug metabolism. It is hoped
that the position will be filled soon. The Department is staffed
by five professors (one vacancy), 16 associate professors
(one vacancy), one assistant professor, three external associ-
ate professors, three senior clerks, 13 laboratory technicians,
DEPARTMENT OF PHARMACOLOGY
PAGE 85
In the year passed Ole Jannik Bjerrum has been
appointed as professor in pharmacology
one temporary laboratory technician, one trainee, three labo-
ratory porters, one assistant and four cleaners. At present 17
PhD students are employed at the Department. In addition
several research assistants and technicians are employed on
grants from external funds. Several staff members (both sci-
entific and technical-administrative staff) have left their posi-
tions for jobs primarily in the pharmaceutical industry.
PROJECTS
NEUROPHARMACOLOGY
GABA as transmitter
The project deals with secretion from the intermediate- and
posterior hypophysis. The existence of numerous neuropep-
tides and neurotransmitters as well as receptors for different
neuroactive substances has been shown in the hypophysis.
In different in vitro systems the pharmacological significance
of neuroactive substances for secretion of hormones is inves-
tigated. In the year passed the GABA-receptors in the hy-
pophysis have been in focus. The influence of different neu-
rosteroids on the GABA-receptors in the hypophysis has
been investigated by means of electrophysiological tech-
niques in slices from rat hypophysis (patch clamp) and on iso-
lated organs. It has been shown, that there are several bind-
ing sites for neurosteroids at the GABA-receptors and that
there are difference in the sensitivity of the receptors in the
intermediate- and posterior hypophysis.
The connection between the pharmacology of GABAA-
receptors and there subunit composition is examined by a
combination of patch-clamp electrophysiology and RT-PCR
analysis of mRNA at single nerve cells. By use of cell cultures
and slices from different part of the brain the regional variation
of the characteristics of the GABA-receptors is examined (co-
operation with F.F. Johansen, Neuropathological laboratory,
University of Copenhagen).
The pharmacology and mechanism of receptoractivation for
partial GABAA-agonists are examined by patch-clamp electro-
physiology in cultures of nerve cells. The effect of substances
with modulating effect at GABAA-receptors (benzodiazepines,
barbiturates, neurosteroids and metalions) is also examined
as well as new substances synthesised at the Department of
Medicinal Chemistry (Cooperation with J.D.C. Lambert, De-
partment of Physiology, University of Århus and researchers
at Department of Medicinal Chemistry, Royal Danish School
of Pharmacy).
(Uffe Kristiansen, Bjarne Fjalland, Bjarke Ebert, Suzanne
Hansen, Henrik Vestergaard, Gunilla Steven)
Communication between the immune
and the neuroendocrine system
The research is dealing with the communication between the
immune and the neuroendocrine system at the neurohy-
pophysial level. In previous experiments we have shown the
ability of interleukin-1� to stimulate the release, both in-vivo
and in-vitro, of oxytocin and vasopressin. At the present we
are investigating the pattern of cytokines release from cul-
tured glia cells from the neurohypophysis (pituicytes) and the
mechanisms which control this release. The main objective is
to elucidate whether a paracrine communication between the
pituicytes and the axonal terminals in the neurohypophysis
exists.
(Jens Juul Dencker Christensen, Erik Wind Hansen, Lise
Moesby, Tine Klavsen, Janne Møgelhøj Colding, Helle
Dyhrfjeld, Betina Schøler)
MOLECULAR PHARMACOLOGY
In collaboration with the neuromedicinalchemical group at the
Department of Medicinal Chemistry the pharmacological
characterisation of new substances at glutamate- and GABA-
receptors is undertaken. The binding profile of new radio-
active glutamate and GABA-ligands is investigated by means
of binding studies in homogenates and receptorautoradio-
grafic methods.
In collaboration with the neuromedicinalchemical group and
the research institute at Merck, Sharp & Domes in England
the connection between the subunit composition of humane
GABA-receptors and the pharmacological profile of a series
of agonists, partial agonists and antagonists is examined.
With the purpose of development of new strategies to treat
neuropathic pain a series of strong analgesics is investigated
in receptorbinding models, isolated organs and electrophysio-
logically with respect to effect on the NMDA-receptors.
(Bjarke Ebert, Martin Mortensen, Bjarne Fjalland, Durita
Poulsen)
ANNUAL REPORT 2000–2001
PAGE 86
Pathophysiological investigation of neuropathic pain
through pharmacological intervention
Pain of nerve injury (neuropathic pain) is difficult to treat.
Preclinical and clinical experiments with analgetica have
shown discrepancy which probably reflecting individual pa-
tient variation in the activation of the pain provoking mecha-
nisms of sensing, transmission and transduction. The goal of
the project is through better knowledge of the patophysiologi-
cal mechanisms to improve the individual treatment regimen.
A set of rat models for neuropathic pain is under establish-
ment for testing with new and well-known antagonists and
agonists for the involved receptor systems.
(Ole J. Bjerrum and Majid Sheykhzade)
Neurotoxic and neuroprotective effects of nitrogen oxide
Nitrogen oxide (NO) is involved in both neurotoxicity and neu-
roprotection depending on where, when, why, how and how
much NO is formed. Thus, NO formed from eNOS under is-
chemia is neruroprotective whereas NO from nNOS and iNOS
under this condition is neurotoxic.
Using primary cultures of cortical neurons and cerebellar
neurons we are studying the formation of NO under different
neurotoxic stress stimuli and trying to correlate the amount or
character of NO formed with cell death or survival. To further
elucidate the mechanism of action we are studying the intra-
cellular targets for NO with special emphasis on mitochondria
as we have found that NO inhibits respiration in neurons.
(Trine Meldgaard Lund, Gunilla Steven, Marianne Michaëly,
Arne Schousboe in collaboration with John Garthwaite, UCL,
UK)
Glutaric aciduria type 1 – a metabolic disease
with neurodegenerative symptoms
Patients with glutaric aciduria type 1 have mutations in the
gene coding for the glutaryl-CoA-dehydogenase enzyme. This
enzyme is essential in the catabolism of lysine, hydroxylysine
and tryptophan, thus an accumulation of the metabolites 3-
hydroxy-glutaric acid, glutaric acid and glutaconic acid is
seen in these patients. The objective of this study is to eluci-
date whether these metabolites are responsible for the neu-
ropatological findings in these patients. Using cultures of cor-
tical neurones we are studying the viability of the cells after
treatment with the metabolites and have found that they are
neurotoxic. We are now in the process of finding the target
for these neurotoxic compounds, this probably being the
NMDA subtype of glutamate receptors, having ruled out any
effect on the other glutamate receptor subtypes and gluta-
mate uptake.
(Trine Meldgaard Lund, Arne Schousboe, Darryl Pickering,
Anders S. Kristensen in collaboration with Allan Meldgaard
Lund and Ernst Christensen, Department of Clinical Genetics,
Copenhagen University Hospital)
Characterization of glutamate receptors
In order to investigate the role of the various AMPA receptors
(AMPA-R) in the normal functioning of the brain (e.g. memory
formation), as well as their role in pathological conditions (e.g.
stroke, epilepsy, Alzheimer’s disease), it would be highly ad-
vantageous to have subtype-selective agonists and antago-
nists. The latter could have potential applications as thera-
peutics.
Using the cloned, recombinant wild-type and mutant rat
AMPA-R (GluR1-4) we have made significant progress in the
last year towards an understanding, at the molecular level, of
the properties of both the receptor proteins and of the ago-
nist chemical structures that can lead to subtype selectivity
and increased affinity and potency. Site-directed mutagenesis
of GluR1 and GluR3 have revealed amino acid residues within
the vicinity of the agonist binding site that are responsible for
controlling both agonist affinity and desensitisation kinetics.
Using this experimentally gained information, we have em-
ployed computer homology modelling of GluR1-4 to predict
new structures of compounds that should have increased po-
tency, affinity and selectivity. In the future, we hope to be able
to increase our current selectivity factor of 125-fold to > 1,000-
fold.
(Darryl Pickering, Anders S. Kristensen, Tue G. Banke and
Arne Schousboe in collaboration with Ulf Madsen, Jeremy
Greenwood and Tommy Liljefors, Dept. Med. Chem.)
Characterization of GABAA receptors
Using Sf9 cells as an expression system the assembly pro-
cess for GABAA receptors has been investigated. In receptors
formed from �1, �2 and �2 subunits it was found that musci-
mol (GABA agonist) binding appears prior to binding of fluni-
trazepam (modulator) or TBPS (channel blocker). Thus, bind-
ing of the agonist may not require a fully formed operational
receptor complex of a pentameric configuration. It was addi-
tionally shown that the �2 subunit plays a key role in the re-
ceptor assembly process. The chimeric subunits �1/�2 and
�2/�1 representing the extracellular N-terminal domain of �1
and �2 subunits, respectively have been used in combination
with �2 and �2�2 to elucidate the significance of these do-
mains for desensitization. The �1/�2 chimara did not exhibit
desensitization after GABA stimulation independent of the
combination with �2 or �2�2. This suggests that the C-termi-
nal segment of the �1 subunit may be important for the de-
sensitization properties. More detailed investigations of site
directed mutagenic receptors may allow identification of the
molecular site involved in the desensitization mechanism.
(Lisbeth Elster, Claus F. Poulsen, Darryl Pickering, Uffe
Kristiansen and Arne Schousboe in collaboration with Dr.
R.W. Olsen, Dept. Mol. Med. Pharmacol., UCLA, Los
Angeles, CA, USA)
DEPARTMENT OF PHARMACOLOGY
PAGE 87
Characterization of GABA transporters
GABA transporters cloned from mouse (GAT1-4) and tran-
siently expressed in HEK cells have been used to study the
subtype selectivity with regard to inhibition of GABA transport
by a number of lipophilic derivatives of exo-THPO. All ana-
logues inhibit GABA transport mediated by GAT1 and a small
number of these also exhibited inhibitory activity for GAT2.
The anticonvulsant activities of exo-THPO has been com-
pared with that of its N-methyl and N-ethyl derivatives previ-
ously identified as inhibitors of neuronal and astrocytic GABA
uptake with differential potency. It was found that the potency
as antivonvulsants in mice prone for audiogenic seizures cor-
relates with the potency of these compounds as inhibitors of
astroglial GABA uptake but not to that as inhibitors of neu-
ronal GABA uptake. The GABA transporters specificity of a
new series of GABA-analogues, amino-cyclohexane car-
boxylic acid derivatives with lipophilic side chains, are now
under investigation. These compounds exhibit a novel phar-
macological profile with regard to inhibition of subtypes of
GABA transporters.
(Orla M. Larsson, Alan Sarup, Darryl Pickering, Lone
Petersen, Helle Dyhrfjeld and Arne Schousboe in collabora-
tion with Bente Frølund, Rasmus P. Clausen and Povl
Krogsgaard-Larsen, Dept. Med. Chem. and Dr. H.S. White,
Dept. Pharmacol., Univ. Salt Lake City, SLC, Utah, USA)
Glutamate metabolism and transport
in neurons and astrocytes
Using cerebellar astrocytes and granule neurones in mono-
and cocultures, 13C- and 15N-labeled glutamine, lactate and
alanine and NMR and GC-MS technology, it has been shown
that transfer of ammonia nitrogen between glutamatergic neu-
rons and astrocytes to some extent can be accounted for by
a lactate-alanine shuttle transporting alanine from neurones to
astrocytes and lactate in the opposite direction. Glutamate re-
leased from neurones is transported into astrocytes via two
different transporters GLAST and GLT-1. The regulation of the
expression of these transporters has been investigated using
specific antibodies and it has been shown that activation of
neurotrophine receptors on the astrocytes plays an important
role in this process. Moreover, it appears that intracellular sig-
naling pathways such as the MAP kinase pathway are in-
volved. Additionally, we have investigated the possibility of us-
ing a newly developed non-transportable glutamate trans-
porter inhibitor threobenzyloxyaspartate (TBOA) as a tool to
distinguish between vesicular and carrier mediated depolar-
ization coupled neuronal glutamate release. It was demon-
strated that TBOA blocks the carrier mediated release without
affecting the vesicular release during K+-induced depolarization
of glutamatergic cerebellar granule neurones in cell culture.
(Helle S. Waagepetersen, Georgi Gegelashvili, Alan Sarup,
Kirsten Thuesen and Arne Schousboe in collaboration with
Dr. U. Sonnewald, Univ. of Trondheim, Norway, Dr. N.C.
Danbolt, Univ. of Oslo, Norway and Dr. Jens Zimmer, Univ.
Odense)
Heterogeneity of astrocytic mitochondrial metabolism
Using 13C-labeled lactate or glucose and subsequent NMR
and GC/MS analysis of samples from astrocytes and their in-
cubation media it has been demonstrated that these two
substrates are differentially metabolized by these cells.
Moreover, it was shown that astrocytic mitochondria are het-
erogeneous since different populations are involved in biosyn-
thesis of releasable citrate and glutamine. A model of four dif-
ferent types of mitochondria with TCA cyclus associated with
metabolism of acetyl CoA derived from exogenously supplied
or endogenuously produced lactate has been proposed.
Further experimentation is needed to shed light on the func-
tional importance of such heterogeneity.
(Helle S. Waagepetersen, Orla M. Larsson, Kirsten Thuesen
and Arne Schousboe in collaboration with Dr. U. Sonnewald,
Univ. of Trondheim, Norway.).
(Tue Banke, Hanne Danø, Lisbeth Elster, Georgi Gegelashvili,
Anders Skov Kristensen, Orla M. Larsson, Lone Petersen,
Darryl Pickering, Claus F. Poulsen, Alan Sarup, Arne
Schousboe, Kirsten Thuesen and Helle S. Waagepetersen)
The cytoprotective role of ER-stress proteins.
The Endoplasmatic reticulum (ER) plays a central role in the
cellular stress response as the structure where protein modifi-
cation, processing and quality control are exerted. In addition,
the ER is the intracellular reservoir for Ca2+, an ion involved in
many signalling reactions, including those mediating the
stress reponse. A protein in the lumen of the ER called
GRP78 (Glucose Regulated Protein or BiP (immunoglobulin
Heavy Chain Binding Protein) is homologous to the cytosolic
chaperone and stress protein HSP70. GRP78 is a member of
a family of stress proteins (including e.g. GRP94, GRP75,
GRP58, GRP170) that all functions as stress proteins. While
the cytoprotective role of the GRP-family, especially GRP78,
is well documented within the fileds of cancer biology and im-
munology very little evidence has been obtained from neuro-
biological research. GRP78 obtains a key positions as a
chaperone protein in connection with the synthesis of ER-
associated ribosomes and protein tanslocation into the lumen
of ER. GRP78 is upregulated significantly on the levels of
mRNA and protein in in vitro as well as in vivo models of
ichemia. This emphasizes the possible cytoprotective role of
GRP78 in ischemia and other conditions involving glutamate
toxicity.
Recently we have observed that a 16 hours pre-treatment
with low, non toxic doses of the EAA NMDA significantly re-
duces the cytotoxic potential of subsequent exposure to toxic
doses of NMDA (the phenomenon of tolerance). This phe-
ANNUAL REPORT 2000–2001
PAGE 88
nomen is accompanied by a significant (up to 80%) upregula-
tion of GRP78. We are currently working on characterization
of the pharmacological basis for the establishement of the tol-
erance. Furthermore, it is investigated whether or not there is
a causal relation between GRP78 and the NMDA mediated
tolerance against glutamate toxicity. Likewise the influence of
GRP78 on EAA mediated Ca2+ signals is investigated.
(Aase Frandsen, Pia Birch Nielsen, Paulo Girao, Arne
Schousboe).
(GRP expression in collaboration with Professor Wulf Pachen,
Dept of Exp neurology, Max-Planck Institute of Experimental
Neurology, Cologne)
The role of cytokines in neurodegeneration
and neuroprotection
New results indicate a common area of function between the
stress activated signalling from the ER and signalling through
TNF p55- receptors (TNFR1). This area arises through an ac-
tivation of the transcription factor NF-�B through an internal
stress stimulus to the ER (EOR, ER overload response). An
externally released NF-�B activation is seen e.g. when TNF
binds to TNFR1. This binding recruits the transduction mole-
cules FADD/MORT1 (FAS associated death domain protein)
and RIP (receptor interacting protein). FADD/MORT1 medi-
ates the proapoptotic effect of TNF whereas the RIP activates
the antiapoptotic effect of NF-�B. In primary cultures from
TNFR1-deficient mice we are currently investigating if changes
in NF-�B (and other pro- and antiapoptotic factors) specifical-
ly can be ascribed to the lack of the TNFR1-receptor or
changes in the EOR.
(Aase Frandsen in collaboration with Prof. Bente Finsen and
coworkers, University of Odense)
The role of IFN� in toxicity induced in CNS
induced by ischemia or inflammation
The sensitivity of nerve cells towards ischemic damage is in-
creased by IFN�. Even though IFN� not normally are found in
association with ischemia in the brain, this finding allows the
possibility that IFN� alone or in combination with e.g. EAAs
and TNF in a fundamental manner may change the suscepti-
bility of the CNS not only to ischemic conditions but also in
connection with leucocyte infiltration in the brain seen in pa-
tients with disseminated sclerosis. Recently, we have demon-
strated that IFN� is potentiating the toxic effect of NMDA and
AMPA in cultured neurons from IFN� deficient mice, and we
are currently investigating the pharmacology of this response.
(Aase Frandsen in collaboration with Prof Bente Finsen and
coworkers, University of Odense)
CUSTOM MADE ANTIBODIES
Generation of recombinant antibodies recognizing
MHC/peptide complexes of relevance for
the pathogenesis of multiple sclerosis
The purpose of the project is to generate antibodies recogniz-
ing specific MHC/peptide complexes of relevance for the
pathogenesis of multiple sclerosis. The strategy is that such
reagents will be useful in modulating the autoaggresive T cell
response. To generate such antibodies we use the so-called
page display technology where the total antibody repertoire of
immunized animals are cloned and expressed in bacterial
cells. The antibody libraries are generated by a PCR (Poly-
merase Chain Reaction) based method and allows for isola-
tion of the wanted specificity through positive selection.
Generation of antibodies that recognize specific
MHC/peptide complexes of relevance for
the pathogenesis of specific melanoma cancers
Studies of melanoma patients have revealed the identity of
activated T cells specific for defined MHC/peptide complexes.
These peptides are derived from tumour associated antigens.
Thus, these MHC/peptide complexes become cell surface
markers for these malignancies. We want to use the techno-
logy described above to generate antibodies specific for
these MHC/peptide complexes since we have shown previ-
ously that such antibodies can be conjugated with cytotoxic
reagents with the effect of killing cells in a MHC/peptide-
specific manner.
DEPARTMENT OF PHARMACOLOGY
PAGE 89
of the three NOS enzymes that is upregulated and their local-
ization. Furthermore, it will give us an increased understand-
ing of the mechanisms underlying an eventual hyper- or hy-
poreactivity of cerebral blood vessels after mental stress.
(Inger Jansen Olesen, Tina Zinck, Majid Sheykhzade, Trine
Meldgaard Lund, Kirsten Busk)
Studies of the effect of glyceryltrinitrate infusion in rat on
nitric oxid synthase in dura and cerebral blood vessels
NO is a powerful vasodilator of general importance for the ar-
terial diameter. It was recently shown that NO is of main im-
portance in the migraine pathogenesis. A 20 minute intra-
venous infusion of glyceryltrinitrate (GTN) induce a migraine
attack fulfilling the criteria for migraine without aura, in mi-
graine patients at an average time of 5.5 hrs after the infu-
sion. Furthermore, L-NMMA, an inhibitor of NOS is effective in
the treatment of an acute migraine attack. The long time lag
of 5.5 hrs from GTN infusion to maximum migraine pain inten-
sity could indicate that NO initiate a slowly progressing patho-
logical reaction, that eventually will lead to a migraine attack.
We have found that after infusion of GTN the synthesis of in-
ducible NOS is upregulated in dura from rat. The maximal
amount of NOS is found 4-6 hrs after the GTN-infusion is ter-
minated, i.e. at the time when the migraine patients develop
the delayed headache (migraine attack). In the following stud-
ies we intend to illuminate changes in the expression also of
endothelial and neuronal nitric oxide synthase (NOS) in dura
and all the three NOS enzymes in cerebral blood vessels after
the infusion of GTN. Furthermore, we will investigate how in-
fusions of GTN involve changes in the sensitivity of cerebral
blood vessels to perivascular transmitters.
The results from the project will lead to an increased know-
ledge about which of the three different NOS enzymes that is
upregulated and where they are localized. Furthermore, we
will collect an increased understanding of the mechanisms
underlying an eventual hyper- or hyporeactivity of cerebral
blood vessels after GTN-infusion.
(Inger Jansen Olesen, Tina Zinck, Majid Sheykhzade, Trine
Meldgaard Lund, Uwe Reuter, Kirsten Busk)
Clinical and experimental micro array
investigations of mRNA expression during migraine
We have in a human model of migraine found a number of
substances that 5-7 hrs after an intravenous infusion trigger a
migraine attack. The key to the understanding of the outbreak
of the migraine attack lie in the mechanisms activated during
the infusion and that hour’s later lead to the migraine pain. If
several substances with different mechanisms of action initi-
ate a migraine attack, they must share a mechanism that is of
vital importance for the development of the migraine attack.
We have in a previous study shown that infusion of glyceryl-
trinitrate (GTN) in the rat results in an increased expression of
PAGE 90
ANNUAL REPORT 2000–2001
Identification of peptides or peptide-like domains that
specifically interact with a protein-protein interface of
relevance for the modulation of blood clotting
We wish to identify small structures that interfere with the
binding of FVIIa to TF using page display technology. This will
be accomplished by searching for small peptides or small
peptide-like domains that utilize the same binding area that
are involved in the protein-protein interaction between FVIIa
and TF. The selection will include page displayed peptide li-
braries comprising both linearly and disulfide-constrained
peptides.
(Jan Engberg, Erik Riise, Liselotte Brix Jensen, Pernille Kops,
Rikke Claussen, Lars Harder Christensen, Rebecca Bach
Jensen and Espen Jannik Bjerrum)
(We collaborate with the groups of professor Lars Fugger,
Dept. of Clinical Immunology, Skejby Sygehus, professor
Jesper Zeuthen and ass. professor Lars Østergård Pedersen,
Dept. of Cell Biology and Cancer Research, The Danish
Cancer Society and research managers Lars Christian
Pedersen and Søren Bjørn, Novo Nordisk A/S)
VASCULAR PHARMACOLOGY
Studies of the effect of mental stress in rat on nitric
oxide synthase in dura and cerebral blood vessels
When patients are asked what triggers their episodes of mi-
graine, the majority of them nominate stress and it is well ac-
cepted that stress heighten the risk of migraine headaches.
The mechanisms underlying stress-induced migraine has still
not been investigated in detail and a possible explanation
could be a stress provoked increase in expression of en-
dothelial, inducible or neuronal NOS.
In this project we intend to illuminate changes in nitric oxide
synthase (NOS) expression in cerebral blood vessels and dura
after mental stress in rat. Furthermore we intend to investi-
gate if mental stress involve changes in sensitivity of cerebral
blood vessels to perivascular transmitters. The results from
the project will lead to an increased knowledge about which
iNOS mRNA in the dura, 2 and 4 hrs after termination of the
GTN infusion, and we have experimental evidence that this
enzyme is involved in migraine attacks.
The microarray technique allows quantifying gene-expres-
sion of thousand of individual mRNA transcripts simultane-
ously. We now plan to investigate the gene-expression after
infusion of a number of migraine provoking substances. The
study will be performed in migraine relevant tissues from rat,
as well as in leucocytes taken during a spontaneous migraine
attack and after experimentally triggered migraine in man. We
hope to be able to narrow the common denominators activat-
ed by all substances down to a few genes and hereby to
map out the genes that are activated in the beginning of a
migraine attack.
(Inger Jansen Olesen, Jes Olesen, Jens D Mikkelsen, Jesper
F Tvedskov, Kirsten Aagaard Busk)
Studies of the effect of feverfew and parthenolide
on nitric oxide synthase activity in cerebral arteries
and dura of guinea pig
Tanacetum parthenium(L) commonly known as feverfew is a
popular herbal remedy advocated for fever, arthritis and mi-
graine. The anti-migraine effect is mainly attributed to ses-
quiterpen lactones present in the plant. Parthenolide, the pre-
dominant sesquiterpen lactone in feverfew is regarded as the
most important of the biologically active substances isolated
from the plant. The exact mechanism by which feverfew and
parthenolide act in order to exhibit prophylactic anti-migraine
effect is still unknown. A number of recent studies indicate
that NO is a crucial molecule for the induction of migraine,
the present study is therefore designed to study the effect of
feverfew and parthenolide on enzymes catalyzing the forma-
tion of NO in cerebral arteries and dura.
(Inger Jansen Olesen, Per Mølgaard, Anne Adsersen, Trine
Meldgaard Lund, Majid Sheykhzade, Kirsten Aagaard Busk)
Signalling pathway for CGRP in isolated
resistance coronary arteries of rat
The intramyocardial resistance arteries regulate the coronary
perfusion. These arteries are densely innervated by sensory
nerve endings containing calcitonin gene-related peptide
(CGRP) and substance P. CGRP is a potent and powerful va-
sodilator, which is released during cardiac ischemia, and low
pH levels indicating an important role for CGRP in regulation
of coronary blood flow under ischemic conditions. The pur-
pose of our study was to investigate the mechanism of action
behind CGRP-induced relaxation in isolated rat intramural
coronary arteries.
Our results clearly demonstrate that CGRP relaxes precon-
tracted rat coronary arteries via three mechanisms: (1) a de-
crease in [Ca2+]i by inhibiting the Ca2+ influx through mem-
brane hyperpolarization mediated partly by activation of the
large conductance Ca2+- activated potassium channels, (2) a
decrease in [Ca2+]i presumably by sequestrating cytosolic
Ca2+ into thapsigargin-sensitive Ca2+ storage sites and (3) a
decrease in the Ca2+- sensitivity of the contractile apparatus.
In resting coronary arteries, however, there seems to be an
interplay between different types of K+ channels.
(Majid Sheykhzade in collaboration with Niels C. Berg Nyborg,
Novo Nordisk A/S)
MICROBIOLOGY
Microbiological control of pharmaceutical products
Pharmaceutical products for parenteral administration must
be free of pyrogens. Pharmaceutical preparations are tested
for pyrogens by the “Test for pyrogens” (rabbit pyrogen test)
or “Test for bacterial endotoxins” (LAL test). Both pyrogen
tests have limitations. Therefore we work towards alternative
in-vitro assays. The monocytic cell line Mono Mac 6 is being
evaluated for its use in detection of pyrogens in pharmaceuti-
cal preparation. In vivo monocytes play a key role in the fever
pathogenesis. When exposed to pyrogens they release cy-
tokines that mediate fever.
Like the rabbit pyrogen test, we have found that the Mono
Mac 6 cells are able to detect a broard spectum of pyrogenic
microorganisms. The cell culture assay is being optimized to
achieve a higher sensitivity to pyrogens.
Spores and vegetative bacteria of the gram-positive Bacillus
subtilis and the cell wall component lipotheicoic acid are able
to induce IL-6 in Mono Mac 6 cells. This makes the Mono
Mac 6 assay a usefull tool to study the thermostability of
these microorgansims and cell wall components.
The Mono Mac 6 assay is a valuable tool to test pharma-
ceutical products for pyrogenic contamination.
(Jens Juul Dencker Christensen, Erik Wind Hansen, Lise
Moesby, Janne Møgelhøj Colding, Helle Dyhrfjeld, Betina
Schøler)
Retroviral membrane fusion
The fusion protein of Moloney murine retrovirus is investigat-
ed. The fusion protein is a transmembrane protein. During
virus maturation a 16 amino acid peptide (the R peptide) is
cleaved of the cytoplasmic tail in order for the fusion protein
to gain activity. The R peptide has the sequence VLTQQY-
HQLKPIEYEP. We have previously found that the R peptide is
palmitoylated.
The R peptide is investigated by mutational analysis, fol-
lowed by transfection of the mutated viral genome into cells.
If the R peptide is totally truncated previous results show a
premature fusion (cell-cell fusion).
R peptide sequences (GenBank) of different murine retro-
virus were compared. The first ten amino acids are well con-
DEPARTMENT OF PHARMACOLOGY
PAGE 91
served whereas the last amino acids varies largely and can be
deleted without serious consequences for the viral life cycle.
We have changed the lysine group (K) (to T or R) as it is a
candidate for the palmitoylation (amide binding). No biological
affects was observed, which either shows that the palmitoyl
group is not located here, or that that the palmitoylation does
not have biological effects.
Deletions in the well-conserved region were made (TQQY-
HQLK deletion, TQQY deletion, QYH deletion and HQLK
deletion). By transfection in cells these all give biological ef-
fects:
The TQQYHQLK deletion gives a premature fusion, does
not produce virus particles and is lethal for the cells. The
smaller deletions all give slight premature fusion, produce
virus particles, which though have a poor replication.
Analysis of protein cleavage is currently being investigated.
(Anne Zedeler, Randi Jensen, Klaus B. Andersen)
BIOACTIVE LIPIDS
Phospholipids are building blocks of the cell membranes, but
phospholipids are also precursors for extracellular and intra-
cellular signaling molecules that function as local hormones
(autocoids) and as second messengers, respectively. Some of
these bioactive lipids are formed from arachidonic acid, which
again is formed from the essential fatty acid linoleic acid. Fish
oils contains long-chain n-3 fatty acids, which can affect the
arachidonic acid metabolism, and the dietary content of n-3
fatty acids can thus affect different biological parameters.
Furthermore, dietary n-3 fatty acids are essential for the de-
velopment of the brain. Other bioactive lipids comprises dia-
cylglycerol, phosphatidic acid, platelet activating factor, lyso-
phosphatidic acid, ceramide, sphingosine-1-phosphate,
phosphatidylinositol 3,4,5-trisphosphate, 2-arachidonoyl-glyc-
erol, anandamide, and N-acyl-ethanolamines. We are current-
ly focusing on understanding the functions of N-acyl-ethanol-
amine phospholipids (NAPE) and of N-acyl-ethanolamines
(NAE) in the brain.
Biochemical characterization of the NAPE/NAE system
We are characterizing the enzymes involved in the formation
of NAPE (N-acyl-transferase) and in the formation of NAE
(NAPE-hydrolyzing phospholipase D). Furthermore, we are
studying the formation of these lipids in cultured neurons and
brain slices, and quantifying NAPE in tissue extracts by nega-
tiv ionisation electrospray mass spectrometer.
NAPE and NAE can be formed in cultured neurons exposed
to excitotoxic concentrations of glutamate or other com-
pounds that can induce cell injury. NAPE is believed to have a
membrane stabilizing effect, and NAPE is formed as a stress
response in cultured neurons and in rat brain in vivo. Some
molecular species of NAE, e.g. N-arachidonoyl-ethanolamine
(also called anandamide) and N-palmitoyl-ethanolamine are
ligands for different cannabinoid receptors, and these two
species of NAE have different biological effects. N-Arachidonoyl-
ethanolamine has the same biological effects as �9-tetra-
hydrocannabinol and N-palmitoyl-ethanolamine has antinoci-
ceptive and antiinflammatory effects. 2-Arachidonoyl-glycerol,
that can be formed during inositol phospholipid turnover, is
also a ligand for the cannabinoid receptors. 2-Arachidonoyl-
glycerol, anandamide and N-palmitoyl-ethanolamine are con-
sidered as endocannabinoids. Thus NAPE may be a neuronal
stress lipid and it is precursor for different endocannabinoids.
(Harald S. Hansen, Birthe Moesgaard, Henrik Hansen, Gitte
Petersen, Grete Sørensen, Jytte Palmgreen in collaboration
with Steen Honoré Hansen (Royal Danish School of Pharmacy),
J.J. Fernandéz-Ruiz (Complutense University, Spain), C.I
konomidou (Humboldt University, Tyskland), and H.H.O.
Schmid (University of Minnesota, USA))
NAPE and NAE in human brain tumors
We are quantifying in human brain tumours the activity of N-
acyltransferase, NAPE-hydrolysing phospholipase D, and
Fatty-Acid-Amide-Hyrdolase, three enzymes that take part in
the turnover of anandamide. Furthermore, we are also quanti-
fying different NAE molecular species. Anandamide and con-
geners may have a function in regulating the growth rate of
brain tumours.
(Harald S. Hansen, Birthe Moesgaard, Gitte Petersen, Jytte
Palmgren, Grete Sørensen in collaboration with M. Kosteljanets
and Helle Broholm (Danish State hospital), and H.H.O. Schmid
and P.C. Schmid (University of Minnesota, USA))
Dietary n-3 fatty acids and human brain development
Harald S. Hansen is engaged in a project on the importance
of dietary n-3 fatty acids for human brain development.
(In collaboration with L. Lauritzen and K.F. Michaelsen
Research Institute for Human Nutrition, Royal Danish
Agricultural and Veterinary University)
ANNUAL REPORT 2000–2001
PAGE 92
DEPARTMENT OF PHARMACOLOGY
SPHERE OF INTEREST
The Department of Social Pharmacy conducts research and
teaching within Social Pharmacy. The Department is also re-
sponsible for interdisciplinary teaching activities, including the
compulsory course on occupational health, the pharmacy in-
ternship and the new postgraduate specialisation programme
in community pharmacy.
Social Pharmacy may be defined as the discipline dealing
with the role of medicines at the level of the individual, group/
organisation and society. Social Pharmacy also embraces the
activities of the pharmaceutical profession. Hence, Social
Pharmacy spans a variety of themes from the experiences
and perceptions of the medicine user to national and interna-
tional drug policy.
Within Social Pharmacy theories and methods from the hu-
manities, the social sciences and natural sciences are applied
in a cross-disciplinary manner.
RESEARCH
The majority of the Department’s research is conducted in in-
terdisciplinary and inter-institutional project groups. Staff
members also participate in or co-ordinate international re-
search projects.
The Department’s research on ‘Medicine Use’ aims at im-
proving the rationality of medicine management and use
among professionals and among users. The goal of the re-
search in ‘Pharmacy practice’ is to support the development
of the pharmacists’ professional role and to evaluate pharma-
cy activities in health care.
TEACHING
Compulsory courses
The teaching of the Department includes the following
compulsory courses:
• Introductory Course (1st term) taught in collaboration
with other departments of The Royal Danish School of
Pharmacy
• Dissemination and Methodology in Social Pharmacy
(3rd term)
• Occupational Health (4th term)
• Social Pharmacy including Management & Organisation
(5th - 6th term)
• Pharmacoeconomics (6th term)
• Drug Dispensing and Customer Communication (7th term)
• Pharmacy Internship (8th term).
Elective courses
Within the period under review the Department taught the
following elective courses:
• Communication and Information
• Pharmacoeconomics
• Research Methods in Social Pharmacy
• Models for Technology Assessment in Health Care
• International Health Care.
POSTGRADUATE PROGRAMME
The Department offers two PhD courses with international
participation and with English as the course language:
‘Methodological Perspectives in Health Services Research’
and ‘Quantitative approaches to the evaluation of health care
inputs’. These courses were not taught in the period covered
by the report.
PAGE 94
Head of Department: Associate Professor Poul R. Kruse, DSc (pharm.)
Department ofSocial Pharmacy
ANNUAL REPORT 2000–2001
Specialisation in Community Pharmacy
The Department is heavily involved in the co-operation be-
tween The Royal Danish School of Pharmacy and Pharmakon
a/s on the new specialisation programme in community phar-
macy. A fuller description of the new postgraduate pro-
gramme is given in a separate chapter, Specialisation in
Community Pharmacy, in the present report. The Specialisation
in Community Pharmacy programme is underway, and the
first Introductory Course was held on 5-9 April 2001 (Ellen
Westh Sørensen and Trine Hopp) and the Course in Health
Care Theory was held on 20-24 August and 20 November
2001 (Ellen Westh Sørensen and Thomas Clemens Jensen).
FKL – THE RESEARCH CENTRE FOR
QUALITY IN MEDICINE USE
The Research Centre for Quality in Medicine Use (FKL –
Forskningscenter for Kvalitetssikret Lægemiddelanvendelse)
was established in 1999. The overall objectives of the centre’s
projects are to provide scientific evidence to optimise the pro-
fessionals’ pharmacotherapy and the population’s medicine
use. In this way the research contributes to improved public
health and quality of life as well as improved economy of the
individual and society. The majority of the Department’s scien-
tific staff are involved in one or more centre projects. The
Centre is directed by Professor Ebba Holme Hansen of the
Department.
The Centre’s approach is multidisciplinary, inter-professional
and inter-institutional. The researchers involved in the Centre’s
activities represent several disciplines and institutions, includ-
ing Pharmakon, the Danish College of Pharmacy Practice, the
County of Vestsjælland, the County of Funen, the National
Institute of Public Health, Copenhagen University, the Univer-
sity of South Denmark, Aalborg University, the University
Hospitals Centre for Nursing and Care Research (UCSF) and
the Institute of Rational Pharmacotherapy. The 1991 Pharma-
cy Foundation has been the major external sponsor of the
Centre’s activities.
The Department’s involvement in FKL-projects is described
under ‘Projects’.
ARRANGEMENTS AND GUESTS
AT THE DEPARTMENT
From 20 September until 24 December 2000, Master’s thesis
students Christian Huyghe and Karen Hoebeke, Vrije
Universiteit Brussels, worked on their Master’s thesis
‘Qualitative and quantitative analysis of the asthma therapeu-
DEPARTMENT OF SOCIAL PHARMACY
Research seminar: ‘Strategies for Dissemination of Pharmaceutical Care Services’ 7-10 June 2001.
PAGE 95
tic outcomes monitoring (TOM) projects’ (advisor: Ellen Westh
Sørensen).
The Department arranged the yearly 2-day course for the
internship pharmacies January 15 to 16, 2001.
Approximately sixty supervisors from community pharmacies
and hospital pharmacies participated.
Professor Th F J Tromp, Groningen Universitet, visited the
Department 27 November 2000.
Dr. Ines Krass, University of Sydney, visited the Department
23 January 2001.
Charlie Benrimoj, Dean, Faculty of Pharmacy and Professor
of Pharmacy Practice, The University of Sydney, visited the
Department 29 January 2001
B.Pharm. (Hons) Mike Rouse from Zimbabwe, visited the
Department 16 May 2001.
Alison Roberts, Honour Thesis student, Faculty of Pharmacy,
The University of Sydney, Australia, studied at the Department
from 1 July until 21 December 2001
Ellen Westh Sørensen and Trine Hopp arranged a research
seminar: ‘Strategies for Dissemination of Pharmaceutical
Care Services’ 7-10 June 2001 at the Department of Social
Pharmacy. Participants in the meeting and presenters: Charlie
Benrimoj, University of Sydney, Alison Roberts, University of
Sydney, Parisa Aslani, University of Sydney, Hanne Herborg,
Division of Research and Development, Pharmakon, Miguel
Angel Gastelurruti, University of Granada, Ellen Westh
Sørensen and Trine Hopp.
Dr. Hans-Rüdiger Elster, Martin-Luther-University, Halle, vis-
ited the Department to discuss student exchange and mutual
research interests on 28 September 2001.
Parisa Aslani, BPharm (Hons), MSc PhD, MPS, MRPharmS,
The University of Sydney, visited the Department for a one
day meeting on 15 October 2001. Parisa Aslani made a pre-
sentation entitled ‘Consumer Opinions on Medicines
Information and Factors Affecting Use’. Trine Hopp and Alison
Roberts made a presentation entitled ‘Development of
Pharmacy Practice with special focus on implementation-pro-
cesses. Project status and theory thoughts’.
The Medicine Consultants Aase Nissen and Helle Neel
Jakobsen as well as Clinical Pharmacist Lisbeth Bregnhøj,
from Copenhagen County, presented their ongoing projects at
a departmental seminar on 17 December 2001.
The Department has hosted several meetings of the FKL –
Research Centre for Quality in Medicine Use throughout
the period of the report.
MEMBERSHIP OF EXTERNAL
BOARDS AND COMMITTEES
EXTERNAL PROFESSIONAL POSITIONS:
Ebba Holme Hansen
• President of the Danish Pharmaceutical Society (until
March 2001)
• Director of the Research Centre for Quality in Medicine Use
(FKL)
• Member of the Council of EUFEPS – European Federation
for the Pharmaceutical Sciences (until March 2001)
• Member of STAC – Scientific and Technical Advisory
Committee of the UNDP/World Bank/WHO Special
Programme for Research and Training in Tropical Disease
• Member of the International Task Force, American Society
of Consultant Pharmacists
• Member of the Project Co-ordinator Network ENRECA –
Enhancement of Research Capacity in Developing Countries
• External evaluator of NEPI, The Swedish National Network
for Pharmacoepidemiology (with Professor PMK Lunde,
Norway)
• Member of the evaluation panel for a professorship in so-
cial pharmacy at the University of Oslo
• Member of the evaluation panel for a professorship in so-
cial pharmacy/pharmaco-economics at the University of
Tromsø
• Member of the Advisory Committee to the Ministry of
Foreign Affairs on children’s and adolescents’ conditions in
developing countries
• Peer reviewer: Pharmacy World and Science, European
Journal of General Practice
• Member of the Editorial Board of Journal of Social and
Administrative Pharmacy
• Member of the Editorial Board of International Journal of
Pharmacy Education.
Trine Hopp
• Board Member of the Section for Social Pharmacy under
the Danish Pharmaceutical Society
• Member of the group ‘Quo Vadis 2000’, Astra-Zeneca
postgraduate training
• Member of Task Force Groups of The Association of
Danish Pharmacists.
Pia Knudsen
• Board Member of The Danish Society of
Pharmacoepidemiology.
ANNUAL REPORT 2000–2001
PAGE 96
Laila Launsø
• Member of the National Board of Health’s Council on
Alternative Treatment
• Member of the Steering Committee of the Disease and
Society - International Network
• Member of the Board of The Danish Knowledge and
Research Centre of Alternative Treatment
• Chairperson of the Research and Knowledge Centre for
Unconventional Cancer Treatment
• Chairperson of the Centre for Bridgebuilding in Health Care
• Research Consultant for European Council for Classical
Homeopathy (ECCH)
• Member of the Treatment Board in the Danish Association
of Sclerosis
• Chairperson of a working group on developing a team of
conventional and unconventional therapists in relation to
treating patients having sclerosis, The Danish Association
of Sclerosis
• Member of the Board for Evaluation of a Homeopathic
Education for Health Professionals, Helsedepartementet,
Oslo
Ellen Westh Sørensen
• External Examiner, Tromsø University, Institute of Pharmacy
• Member of the Course Committee of the Specialisation in
Community Pharmacy
• Member of the Scientific Committee for the 12th
International Social Pharmacy Workshop 2002
• Member of the Supervision Group for the project The
Consultative Pharmacy, carried out by the Research and
Development Department at Pharmakon a/s
• Member of the Editorial Board of the International Journal
of Pharmacy Practice
• Member of the Committee for Postgraduate Training of
Pharmacists (PUF-A)
• Member of the board ‘Interdisciplinary Communication
Course, Copenhagen’
• Member of the Organising Committee for the Forum of
Health Care Research meeting October 2001.
Janine Morgall Traulsen
• Officially appointed external examiner for Engineering and
Social Studies
• Member of the Advisory Board: The Danish National
Institute for Medical Technology Assessment, Ministry of
Health
• Adjunct Professor – Mercer University Southern School of
Pharmacy.
GRANTS
Ebba Holme Hansen has received:
DKK 2.347 million (2000) and DKK 903,000 (2001) from The
Danish Ministry of Foreign Affairs towards the continued
implementation of a research education programme to devel-
op primary health care research in Nepal. In collaboration with
Department of Social Pharmacy; Department of Psychology
and Department of Public Health, University of Copenhagen;
DSI • Danish Institute for Health Services Research and
Development; Department of Epidemiology and Social
Medicine, University of Aarhus; and Tribhuvan University,
Kathmandu.
On behalf of FKL – Research Centre for Quality in Medicine
Use, Ebba Holme Hansen received a grant of DKK 2.5 million
from The 1991 Pharmacy Foundation for co-ordination and
administration and the following projects: The Pharmacy-
University Study, co-ordinated by Ellen Westh Sørensen and
Lotte Stig Haugbølle, and Improved Self-medication and Self-
care co-ordinated by MSc (pharm) Hanne Herborg (Pharma-
kon).
Erik Knudsen, Vestsjællands Amt, in collaboration with
Ebba Holme Hansen, has received DKK 200,000 (2000) and
DKK 338,500 (2001) from the Danish Medical Research
Council’s Regional Fund for Eastern Denmark for the FKL
project: The research foundation for intervention strategies to-
wards medicine prescribing and use. (The grant is adminis-
tered by Vestsjællands Amt).
Ebba Holme Hansen is member of the project group
‘Clinical pharmacist in primary health care’ co-ordinated by
Bente Kirkeby that has received a donation of DKK 700,000
from The 1991 Pharmacy Foundation. (The grant is admin-
istered by Frederiksborg Amt).
Claus Møldrup has received DKK 1,111 million from the
Centre for Evaluation and Health Technology Assessment,
The National Board of Health in support of a post-doc
study on pharmacogenomics.
Ellen Westh Sørensen received DKK 100,000 from The
Hørslev Foundation for the FKL project Pharmacy-University
Study for the period 2001-2002.
PROJECTS
MEDICINE USE
Intentions, Values, Rationales and
Strategies in GPs’ Prescribing
The knowledge assembled in the literature about GPs’ inten-
tions, values, rationales and strategies when prescribing
drugs is sparse. An understanding of the GPs’ perspective is
DEPARTMENT OF SOCIAL PHARMACY
PAGE 97
essential in the attempt to develop primary care. The purpose
of this PhD project is to obtain an understanding of the reality
GPs face when prescribing drugs, from the GPs’ own per-
spective. In order to achieve this, participant observations
and semi-structured interviews are used. An approval from
the local ethics committee has been obtained. Twenty-four
GPs from the County of Vestsjælland have agreed to attend
the study. Both data collection and analysis are made after
the principles of Grounded Theory. The project will finish dur-
ing the spring of 2003.
The project is affiliated with FKL - Research Centre for
Quality in Medicine Use.
(Kristin Eskildsen. Supervised by Ebba Holme Hansen (main
supervisor) and Professor Uffe Juul Jensen, University of
Aarhus).
Prescribing of Antibiotics in Iceland
This project explores general practitioners’ views, reflections
and strategies when dealing with infections and prescribing
antibiotics. The project springs from a former PhD study at
the Department.
(Ebba Holme Hansen in collaboration with Ingunn Björnsdóttir,
CEO, PhD (pharm), and Almar Grímsson, MSc (pharm),
Iceland).
Behaviour of Rural Mothers in
Response to Diarrhoea in Children
Diarrhoea is one of the most common causes of child mortali-
ty in developing countries. Plenty of interventions have aimed
at disseminating and improving the use of ORS (Oral
Rehydration Salt) in relation to diarrhoea, however, without
sufficient success. This project aims at studying the user side
of the issue by exploring the mothers’ perceptions and views
re symptoms and treatment of diarrhoea in children. The pro-
ject springs from a Master’s of Social Pharmacy thesis.
(Ebba Holme Hansen in collaboration with Farai
Chinyanganya, MSc, PhD, United Kingdom).
Popular Attitudes to Medicines and Medicine Supply
The literature in the social sciences is scarce on how different
segments of the population view the benefit of medicines and
the medicine supply system. This project analysis the Danish
population’s perceptions of what constitutes a medicine and
attitudes and behaviours re the benefit of medicines and
herbal remedies, where they should be available, information
during the purchase situation, etc. The data were collected as
part of the Danish Health & Illness Survey year 2000 and cov-
ers large representative national samples of Danes. The sur-
vey provides the opportunity to relate data on the attitudes to
a number of population characteristics including illness,
medicine use, health care utilisation, and life style. The results
of the project will contribute to the user perspective on quality
management in the health care. Furthermore, there will be a
contribution to the development of policy in the drug arena.
The project is affiliated with FKL – Research Centre for
Quality in Medicine Use.
(Ebba Holme Hansen in collaboration with Niels Kr.
Rasmussen, National Institute of Public Health).
Medicine Use among Children and Adolescents
Medicine use is one of the domains studied in the WHO pro-
ject, Health Behaviour in School-Aged Children (HBSC). The
study comprises a series of cross-sectional school surveys of
national representative samples of girls and boys aged 11, 13
and 15. The project started in 1987. Twenty-eight countries
and more than 120,000 respondents participated in the 1998
survey. The study analyses the use of medicine in relation to
sex, age and country over time. Analyses include associa-
tions between medicine use and symptoms, social status,
psychosocial conditions and social network.
The project is affiliated with FKL - Research Centre for
Quality in Medicine Use.
(Ebba Holme Hansen in co-operation with the national co-or-
dinators for the HBSC project: Bjørn Holstein and Pernille
Due, Institute of Public Health, Copenhagen University, and
the international HBSC Co-ordinator Candace Currie,
University of Edinburgh).
TUPP – The User Perspective on Psychotropic Drugs
TUPP was initiated by the European Drug Utilisation Research
Group, formulating the need for qualitative pan-European re-
search on medicine use. The overall objective of the project is
to explore the social meanings attached to the use of psy-
chotropic medicines at different locations in Europe. The core
project is based on qualitative in-depth interviews with at
least 20 informants in each country. As the consumption of
SSRIs is increasing rapidly all over Europe, the study of these
medicines is mandatory for each research group. A multidisci-
plinary project group with participants from 11 countries and
13 research groups has been established.
The Danish sub-studies are affiliated with The Research
Centre for Quality in Medicine Use.
(Ebba Holme Hansen, Project Co-ordinator, Søren Troels
Christensen, Kristin Eskildsen, Stig Helweg-Jørgensen and
Pia Knudsen in co-operation with approximately 25 re-
searchers from European countries and WHO EURO,
Pharmaceuticals Programme).
Danish sub-studies:
Psychotropic Drug Dependency in a User Perspective
This project explores the users’ experiences, reflections and
strategies in relation to long-term use and being dependent
on psychotropic drugs. The analyses are based on 50 in-
ANNUAL REPORT 2000–2001
PAGE 98
depth, semi-structured interviews with people with a self-di-
agnosed dependence on benzodiazepines, primarily.
(Ebba Holme Hansen and Stig Helweg-Jørgensen).
Young Women’s Use of SSRIs
The objective of this PhD study is to contribute to an under-
standing of the use of SSRIs among younger women by ad-
dressing the users' subjective experiences. The empirical
foundation of the project consists of Danish women aged 18
to 34 with SSRI prescriptions. The women were identified
through pharmacies located in the Copenhagen area. A total
of twelve in-depth interviews including six re-interviews were
conducted.
It can be concluded that the users of SSRIs relate the use
of the medicine not so much to clinical conditions as to social
meanings. It can further be concluded that the use of SSRIs
is related to ambivalent feelings. The medicine is experienced
as a helper that enables the users to regain their social func-
tioning, and at the same time as a labelling agent. This study
showed that the use of SSRIs has more implications than just
controlling the illness. The use of SSRIs has social meanings.
It stigmatises the users, and it has an effect on the users’
self-concept.
The study is linked to TUPP - The User Perspective on
Psychotropic Drugs and to FKL - Research Centre for Quality
in Medicine Use.
(Pia Knudsen supervised by Ebba Holme Hansen (main su-
pervisor) and Janine Morgall Traulsen).
Enhancement of Research Capacity in Nepal:
A Primary Health Care Project
The background for this Danida sponsored project is partly
the Nepalese research system’s lack of competence and ca-
pacity in terms of primary health care, including drug use, and
partly the widespread problems that characterise Nepalese
health care in relation to an overwhelming morbidity level and
an extremely poorly functioning health care. The project
therefore has two main goals.
- To strengthen the research competence at university level in
Nepal through the accomplishment of research courses and
education up to PhD level.
- To focus PhD projects towards primary health care in Nepal,
and to use the results directly as a part of the Nepalese
health policy and in health care practice.
The objective of the project is to integrate two parallel pro-
cesses of development namely a researcher training pro-
gramme and an inter-disciplinary research programme, that
has primary health care as its research agenda.
The PhD studies carried out with the Department deal with
the projects: Quality Assessment of a Health Care Information
System: A Case Study from Nepal (Sharad Onta), Assessing
the Quality of the Provision of Antibacterials in the Nepalese
Health Care System (Shiba Karkee), and A User Perspective
on Tuberculosis Treatment (Pranaya Mishra).
(Ebba Holme Hansen (Project Co-ordinator), Ib Bygbjerg,
Institute of Public Health, University of Copenhagen, Rolf
Kuschel, Department of Psychology, University of Copen-
hagen, and Svend Sabroe, Department of Epidemiology and
Social Medicine, University of Aarhus. The Nepalese counter-
parts are the following professors from the Tribhuvan Univer-
sity, Kathmandu: Mathura P Shrestha, Kumud K Kafle,
Rishikeshab R Regmi, and Ayan B Shrestha. The project is
associated to the Danish ENRECA programme (Enhancement
of Research Capacity in Developing Countries)).
Health Interview Surveys in Europe (EuroHIS); Medicine Use
EuroHIS is a WHO co-ordinated European project aiming at
the development of standardised questionnaires to be used in
national and cross-national health surveys. In this sub-study
nationally used questionnaires dealing with medicine use are
collected and reviewed. Based on the findings, a battery of
questions are developed and validated to form the basis for
future national and international surveys. Researchers from
five countries and the WHO participate in the medicine use
project. The collaborative work is funded by a BIOMED grant
from the EU.
(Ebba Holme Hansen in co-operation with researchers from
Finland, Greece, Israel and WHO EURO).
DEPARTMENT OF SOCIAL PHARMACY
Prevalence of
symptom related
medicine use dur-
ing the past month
among 15-year-old
Danes (percentage
of respondents).
Medicine for headache, 15-year-olds:
Medicine for stomacache, 15-year-olds:
PAGE 99
CEEMedicines
This project aims at mapping and analysing the medicine
markets in Eastern European countries. Data on registered
medicines on the market in each country are collected. The
project is financially supported by the EU and co-ordinated by
Dr. Pietro Folino-Gallo, Università Cattolica del Sacro Cuore,
Rome.
(Ebba Holme Hansen in co-operation with researchers and
medicine regulators from ten countries and WHO EURO,
Pharmaceuticals Programme).
Social Determinants of Medicine Use
in the Danish Population
The aim of this study is to characterise the medicine use of
the Danish population with special focus on social inequality.
The analyses use data from The Danish Health and Illness
Survey 2000 conducted by the National Institute of Public
Health. This interview survey of the population contains social
and demographic background information as well as informa-
tion on health and illness behaviour and self-reported use of
medicine. The analyses will include multivariate analyses and
different therapeutic groups of medicine.
The project is affiliated with FKL - Research Centre for
Quality in Medicine Use.
(Merete W. Nielsen, PhD student, is supervised by Ebba
Holme Hansen (main supervisor) and Niels Kristian
Rasmussen, National Institute of Public Health).
The Practices of Dispensing and
Non-Dispensing Doctors
The number of dispensing doctors has increased world-wide
in recent years. What are the implications of this trend, what
are the consequences for the quality of medicine therapy?
This PhD project aims at evaluating and comparing the pre-
scribing practices of dispensing and non-dispensing doctors
and to assess the quality of dispensing doctors’ pharmacy
practices. Data have been collected.
(Birna Trap, PhD student, MSc (pharm), BCom, under the
supervision of Ebba Holme Hansen (main supervisor), Hans
Hogerzeil, WHO HQ/Geneva, and Charles Todd, University of
Zimbabwe).
A User-evaluation of Treatment with Conventional
Drug Therapy and Classic Homeopathic Treatment
Concerning Allergy and Asthma
(Laila Launsø and Charlotte Grum, MSc, Psychologist;
Henriette Brender, BA, Centre of Bridgebuilding in Health
Care, Copenhagen; Anne Hvenegaard, MSc, Project
Manager, DSI, Institute for Health Care, Copenhagen.
Cooperation with Vinjar Fønnebø, MD, Professor and Director
of Research Centre in Alternative Medicine, University of
Tromsø, Norway)
The Development of Drug Therapy in Denmark
The project is a historical analysis of the factors, including reli-
gious, philosophical, scientific, technological and legal as-
pects, which have determined the development of drug thera-
py in Denmark since the introduction of the concept of autho-
rized drugs in the 17th century.
(Poul R. Kruse).
Cancer Patients’ Use and Assessment
of Herbal Medicine
A survey study on 395 cancer patients’ patterns of usage of
herbal medicine is conducted. The primary aim of the project
is to establish a database to which cancer patients and thera-
pists have access.
(Laila Launsø and The Research and Knowledge Centre for
Unconventional Cancer Treatment: Helle Andersen, MSc;
Louise Rønnov, BA; Henrik Langgaard MD)
Social, Ethical and Legal Aspects
of Pharmacogenomics
This research project focuses on pharmacogenetics and
pharmacogenomics as a research strategy for future drug re-
search and development. The aim of the project is to investi-
gate the pros and cons of pharmacogenomics in a post-mar-
keting perspective with focus on the social, ethical and legal
dimension.
(Claus Møldrup)
Evaluation of a New Drug Distribution Legislation
in Iceland – a European Laboratory
A new drug distribution law took effect in Iceland in 1996.
The main thrust in this legislation is the right of all registered
pharmacists to open one pharmacy each and the abolish-
ment of the drug price regulation by the government and
abatement of the strict rules governing drug advertising to the
public. A multi-study evaluation of the effects of the change in
legislation was initiated in 1995. Various research methods
were employed, including focus group interviews with users
of pharmacy services, interrupted time series analyses of eco-
nomic and drug utilisation data, and focus group and one-on-
one interviews with pharmacists. Data collection and analysis
was completed in 1999. In 2000 and 2001 the results of this
evaluation were prepared in the form of articles.
(Janine Morgall Traulsen, Anna Birna Almarsdóttir, Iceland,
Almar Grímsson, Iceland, and Ingunn Björnsdóttir, Iceland)
The New Medicine Consumer
The goal of this project is to investigate social and economic
trends, which are currently affecting medicine users – attitudes,
knowledge and action. The project focuses on theory devel-
opment as well as data collection. A literature review began
at the end of 2001. The empirical part of the study is being
ANNUAL REPORT 2000–2001
PAGE 100
planned and will include individual interviews and focus group
interviews. Janine Traulsen received a "research stipend" from
DFH beginning September 2001 to develop this project. From
1st October 2001 a PhD student, Bertel Rüdinger, joined the
project).
The project is affiliated with FKL - Research Centre for
Quality in Medicine Use.
(Janine Morgall Traulsen).
Popular Beliefs about Medicine
Eight focus group interviews were carried out in urban and
rural Iceland to answer the research question – What are the
hopes and fears of the lay public in Iceland with regard to
pharmaceutical R & D including issues pertaining to the
Health Care Database? Iceland was chosen to study this
phenomenon in the wake of the public debate about the
Icelandic Health Care Database (the aim is to code medical,
genealogical and genotypical information on the entire popu-
lation). The project consists of a literature review, theory build-
ing and focus group interviews followed by individual inter-
views. Data collection took place in 2001 and analysis and re-
port writing will take place in the first half of 2002.
(Responsibility for carrying out the project lies with a project
group: Janine Morgall Traulsen, Ingunn Björnsdóttir (principal
investigator), Iceland, and Anna Birna Almarsdóttir, Iceland).
PHARMACY PRACTICE
The Distribution of Medicine in Denmark
– in the Light of Deregulation
On 30 May 2001 the members of the Danish Parliament
agreed to deregulate the distribution of medicine to the pub-
lic. The main change is that a wide range of OTC-medicine
(e.g. painkillers and laxatives) can be sold outside pharmacies
beginning 1 October 2001. In the future OTC-medicine will
become part of the normal sale of convenience goods. The
deregulation is a climax of many years of ongoing discussions
concerning how to regulate the distribution of medicine in
Denmark. Having in mind the general advance of market ori-
entated health reforms in western societies one could won-
der: Why has the Danish pharmacy sector not been subject
to deregulation before? And why only deregulate the sale of
OTC-medicine? The PhD project will contribute with know-
ledge of the mechanisms that influence policy processes in
this area.
The project is affiliated with FKL - Research Centre for
Quality in Medicine Use.
(Jakob Bjerg Larsen supervised by Janine Morgall (main su-
pervisor), Poul R. Kruse and Assistant Professor, MSc (pol
sci), PhD Karsten Vrangbæk, Department of Political Science
and Institute of Public Health, University of Copenhagen).
Pharmaceutical Care in Denmark
In Denmark and internationally, the structure of medicine sup-
ply has been discussed during the past 30 years. The role of
the community pharmacist has been a focal point of this dis-
cussion. Pharmaceutical Care has been one of the strategies
used to ensure a professional role for the pharmacist in the
future. The aim of this PhD project is to analyse the founda-
tion for and implementation of Pharmaceutical Care in Danish
community pharmacies. Empirical data have been collected
by a postal questionnaire involving all Danish pharmacies.
The project is affiliated with FKL - Research Centre for
Quality in Medicine Use.
(Charlotte Rossing supervised by Ebba Holme Hansen (main
supervisor) and Janine Morgall Traulsen).
Professional Development of Pharmacy Practice
– with special focus on implementation processes
There are different traditions for carrying out intervention re-
search in the various professional groups. Descriptive and ef-
fectiveness studies dominate. The overall purpose of this PhD
project is to describe and understand the relationships that
influence the implementation process of professional interven-
tions within pharmacy practice in Denmark. The study is car-
ried out from an organisational perspective. This perspective
is necessary in order to follow and analyse the intervention
process and in order to understand possible reasons for
problems in relation to implementation.
The PhD project is part of a bigger international project with
the overall aim ‘Development of strategies for dissemination
of pharmaceutical care services’. Through collaboration with
PhD student Alison Roberts, University of Sydney, the de-
scriptions and understandings of the relationships that influ-
ence the implementation process will be achieved through
quantitative studies as well as qualitative studies.
The project is affiliated with FKL - Research Centre for
Quality in Medicine Use.
(Trine Hopp under the supervision of Ellen Westh Sørensen
(main supervisor), MSc (pharm) Hanne Herborg, Pharmakon,
and Dr. PH Lis Wagner, UCSF. The international project group
includes from the University of Sydney, Australia: PhD student
Alison Roberts under the supervision of Professor Shalom
(Charlie) Benrimoj (main supervisor), Parisa Aslani, Lecturer;
Tim Chen, Lecturer; and Kylie Williams, Lecturer).
The Pharmacy-University Study - an action
research project involving the pharmacy, pharmacy
students and researchers in pharmacy practice
The project is carried out in co-operation between re-
searchers from the Department of Social Pharmacy, re-
searchers from Pharmakon, supervisors in the pharmacies
and pharmacy students during their internship in the pharma-
cies. The project was initiated in 1998 has run for a three-
DEPARTMENT OF SOCIAL PHARMACY
PAGE 101
year period, first year involving the angina pectoris patients,
second year type 2-diabetes patients, third year asthma pa-
tients. The overall purpose of the project is to contribute to
quality development of pharmacy practice and pharmacy
practice research in the area of pharmaceutical care. The
aims of the project are threefold:
• to form the basis of an improvement of the pharmacy’s ad-
vice to patient groups, based on the user perspective, and
to contribute to a basis for decisions for the individual phar-
macy’s policy concerning the patient group
• to develop and test participatory action research as a way
of developing pharmacy practice
• to support the pharmacy students during their internship in
pharmacy work with pharmaceutical care, achieve a good
understanding of the user perspective and get experience
in pharmacy practice research.
During 1999, 2000 and 2001, data have been collected in the
form of interviews with the following patient groups: angina
pectoris patients (123), type 2 diabetes patients (176) and
asthma patients (80). At the same time, through question-
naires, the pharmacy staff has brought out their knowledge
and desire for information concerning the same patient
groups. In 1999, 2000 and 2001, results from the patient in-
terviews and the staff questionnaires were presented to the
staff of the participating pharmacies (1999: 40 pharmacies,
2000: 50 pharmacies, 2001: 28 pharmacies), and the current
activities of the pharmacies were recorded. The activities in
the pharmacies, from all the three years, will be evaluated.
Internship students have been responsible for the interviews
and the organization of tasks on the premises of the partici-
pating pharmacies. The materials of the project can be found
on the internet www.dfh.dk/dfh-apotek/.
Part two (2001-)
The results from the three patient groups uncovered a great
quantity of drug related problems. Therefore, the project
group has decided to carry out a new phase of the project
(second phase). The objective of the second phase is dis-
semination of the results, in an easily accessible form, to the
interested parties in the health sector (patient associations,
pharmacies, MDs, outpatients’ clinics, the counties pharma-
ceutical consultants) as a contribution to their work with im-
proved medicine use to these selected patient groups.
The project is affiliated with FKL - Research Centre for
Quality in Medicine Use.
(Ellen Westh Sørensen and Lotte Stig Haugbølle in co-opera-
tion with Anette Mühring, Hørsholm Apotek; Birgitte
Gundersen, Delfin Apoteket; Hanne Herborg, Pharmakon A/S;
Hanne Lindegren, Ringsted Apotek; Karen Aarestrup
Johansen, The Danish Pharmaceutical Association; Kirsten
Holme Petersen, Pharmakon A/S; Kirsten Laursen, Ørne
Apoteket; Kirsten Lindholm, Centralapoteket, Fyns Amt; Lene
Lorentzen, Frederiksværk Apotek; Linda Larsen, Pharmakon
A/S; Liselotte Winther, Hvalsø Apotek; Thomas Clemens
Jensen, The Royal Danish School of Pharmacy; Trine Toft,
Sygehusapoteket, Vestsjællands Amt; Ulla Ander-sen,
Apoteket Rosen; and pharmacy students from The Royal
Danish School of Pharmacy Camilla Suensen, Eva Awad, Ida
Jensen and Søren Holm-Møller).
Improved Self-medication and Self-care
The objectives of the project are: 1) To develop and imple-
ment service for systematic counselling on self-care and self-
medication in community pharmacies aimed at empowering
users to make decisions and solve problems in order to ob-
tain better quality of life. 2) To develop a model for a con-
trolled study aimed at documenting the outcomes of the ser-
vice and testing the instruments for data collection.
The pilot study was completed in 2001, and the main study
has started. The project is part of an international research
co-operation, Pharmaceutical Care Network Europe (PCNE).
In Denmark, a preliminary study is carried out where the inter-
vention is developed and tested.
The project is affiliated with FKL - Research Centre for
Quality in Medicine Use.
(Project Manager: Hanne Herborg, Pharmakon. Other mem-
bers of the project group: Ellen Westh Sørensen; Steffen
Jarlov, GP; Bertil Marklund, Med.Dr. Project Co-ordinators:
Birthe Søndergaard, Bente Frøkjær, Dor-the Tomsen and
Dorte Glintborg Nielsen).
ARTFARM. Nordic Database for Studies
and Projects within Pharmacy Practice
The objective is to procure relevant Nordic scientific studies
for practitioners and students of pharmacy practice. The main
goal is to be an incentive to research on pharmacy practice.
www.dfh.dk/artfarm.The project is supported financially by
the Danish Pharmaceutical Association.
(Ellen Westh Sørensen in co-operation with Inger Duus
Nielsen, MSc (pharm) and Karen Aarestrup Johansen, MSc
(pharm), Danmarks Apotekerforening; Kirsten Holme Petersen
MSc (pharm) Pharmakon; Susanne l. Weng, MSc (pharm),
Hirtshals Apotek).
Intervention in Pharmacy
– a Case Study about the Implementation
of Pharmaceutical Care at Brønshøj Apotek
The development and implementation of pharmaceutical care
in a community pharmacy has been followed over a period of
2-3 years. The proprietor, the staff and a research consultant
have developed ‘tools’ for the implementation of pharmaceu-
tical care in community pharmacy. The development- and im-
plementation process has been followed. The theoretical ba-
sis is organisation theory. The design is participatory action
research and formative evaluation. Data collection methods
ANNUAL REPORT 2000–2001
PAGE 102
PhD students Trine
Hopp, of the
Department, and
Alison Roberts,
University of
Sydney, analysing
their pilot study:
Development of
Health Care
Services in
Pharmacy Practice.
were interviews of staff and research consultant and docu-
ments from the pharmacy. The change strategy and the barri-
ers and facilitators for the development and implementation of
the new practice is described.
(Ellen Westh Sørensen in co-operation with Research
Consultant Liselotte Winther, Pharmakon, and Pharmacy
Proprietor Inge Børsting and staff at Brønshøj Apotek).
OTHER PROJECTS
A User-evaluation of Medicine, TCM Acupuncture and
Nutrition Therapy concerning Patients having Bronchial
Infections/Symptoms
(Laila Launsø and Eva Brendstrup, MSc, Centre of Bridge-
building in Health Care, Copenhagen).
Bridgebuilding in Health Care
A concept for bridgebuilding in health care between pharma-
cists, physicians and alternative therapists has been devel-
oped including research projects. The focus has been on
conceptualising the practitioners’ treatment models consisting
of four components: disease/health theories; diagnostic sys-
tems; treatment methods and expected and experienced out-
comes. The results are used in relation to seminars focusing
on building dialogues and co-working between conventional
health care groups and alternative therapists.
(Laila Launsø and therapists and researchers from Centre for
Bridgebuilding in Health Care and from The Research and
Knowledge Centre for Unconventional Cancer Treatment and
senior students from University of Roskilde, University of
Copenhagen and Department of Social Pharmacy, The Royal
Danish School of Pharmacy).
Physicians and Pharmacists
Practising Unconventional Treatment
A study has been conducted on 20 physicians’ and pharma-
cists’ motives for education and practice in unconventional
treatments, their experiences from practising both conven-
tional and unconventional treatments and their experience
with reactions from professional colleagues.
(Laila Launsø).
A User-evaluation of Unconventional
and Conventional Cancer Treatment
(Laila Launsø and Henrik Langgaard, MD; Charlotte Kira
Kimby, MSc; Louise Rønnov, BA, The Research and
Knowledge Centre for Unconventional Cancer Treatment;
Inge Henningsen, MSc, Associate Professor, Department of
Statistics, University of Copenhagen).
Evaluation of Community Involvement
in Schistosomiasis Control
More than 200 million people worldwide are affected with
Schistosomiasis, a debilitating long lasting tropical disease. In
Zimbabwe, a community participation project has utilised the
dried berries from a locally grown plant as molluscicide. The
plant is Phytolacca dodecandra - locally called Gopo. The
present PhD project has evaluated the above community par-
ticipation project by analysing attitudes, behaviours and
knowledge as well as learning, gender and power issues.
(Addmore Ndeka, PhD, MA (Sociol). Supervisors: Ebba
Holme Hansen (main supervisor), Per Mølgaard, Department
of Medicinal Chemistry, Peter Furu, Danish Bilharziasis
Laboratory, and Dr. Godfrey Woelk, University of Zimbabwe).
DEPARTMENT OF SOCIAL PHARMACY
PAGE 103
The DanishPharmaceutical Library
THE LIBRARY
The aim of the Library is to support research and education
at the Royal Danish School of Pharmacy and serve the needs
of the School's staff and students. Part of the national net-
work of research libraries, it is open to the public and invites
all interested users to benefit from its traditional and electronic
collections.
The Library provides training and guidance in the use of its
services and how to seek information in the school's net-
worked databases and on the Internet.
The Information Officer is attached to the library’s admini-
stration.
ACTIVITIES AND PROJECTS
The library board and library staff have thoroughly discussed
and evaluated the library’s service profiles and strategies
through 2001.
During the period September 2000 - December 2001, the
library has improved its range of services and information
about the services. Transformation to the electronic library is
actively underway e.g. downloading full-text articles from the
library’s range of electronic journals reached 21,000 articles,
an increase of 100% from December 2000 to December
2001. Students and researchers have the benefit of direct
reservation and request of copies or books through the li-
brary’s OPAC. Interlibrary loan requests are received by e-mail
or the facilities in bibliotek.dk.
Many tests of electronic databases and reference works are
facilitated through the home page of the library: Internet edi-
tion of the Combined Chemical Dictionary, Nature full-text edi-
tion, Pharma-Transfer, Landolt-Börnstein, Encyclopaedia Bri-
tannica - just to mention a few.
The library’s home page was expanded and improved
through autumn 2001. It now provides access to an automat-
ically generated list of new books; LIST-FARM - a holding list
of printed journals in the library; an automatically generated
alphabetical list with links to the electronic journals the library
subscribes to; an annotated web-guide; help-sheets to ac-
cessible databases and much more.
The user survey made it clear that an increase in opening
hours was necessary. The library extended the opening hours
by 4 hours every week starting September 2001.
The merging of the Dictionary of Organic Compounds,
Dictionary of Natural Products and other electronic dictionar-
ies made the library upgrade its access to the networked edi-
tion called the Combined Chemical Dictionary November
2000. The upgrade ensures direct access to information from
laboratories and classrooms.
In December 2000 the library took out an Internet subscrip-
tion to the citation database Web of Science and from
January 2001 access was opened to Science Direct, ensur-
ing access to approx. 1200 electronic journal titles from
Elsevier.
The library system ALEPH was upgraded September 2000,
which gave rise to a good deal of trouble for both library staff
and library users.
Also in 2001 the Danish Pharmaceutical Library participated
actively in several projects concerning "Denmark’s Electronic
Research Library" (DEF), e.g. the library is still part of the pro-
ject to convert the old card catalogues to electronic media.
From August 2000 Alice Nørhede headed a DEF project in-
cluding four other libraries to develop a user survey based on
the international accepted model for European Customer
Satisfaction Index (ECSI). In February 2001 the questionnaire
was distributed to the users of the five libraries and in summer
2001 the results were presented to the board of DEF.
The project generated interest as well as appreciation from
the library society. A report is available on:
http://www.dfh.dk/bibliotek/brugertilfredshed_rapport.php3e
ANNUAL REPORT 2000–2001
PAGE 104
Head of Library Services: Alice Nørhede
Facilities of DADS (Denmark Article Database Service) - a
gateway to electronic journals used intensively by in-house
researchers and students - was much improved in the begin-
ning of 2001. Unfortunately, the library had to terminate ac-
cess in December 2001 due to a 100% increase of the sub-
scription price to the system. Termination started a flood of
protests from researchers and students at the Royal Danish
School of Pharmacy, but there does not appear to be a solu-
tion at this time.
Approx. 35,000 visits were paid to the library from January
2001 to December 2001.
TEACHING AND GUIDANCE
Study Start programme: Since the start of a new structure for
the Study Start programme in 1998, the library has participat-
ed in introduction courses for new students. In September
2000 and 2001 the library offered all new students a lecture
on how to use electronic services in the Danish library sys-
tem, a hands-on lecture on using the Internet for information
retrieval and a tour of the library – presented in 2001 in the
guise of a treasure hunt. Students then carried out compulso-
ry exercises. Both students and library staff evaluate this
training every year and every evaluation results in further ad-
justment and updating of the programme presented.
The library participates in teaching the compulsory course
in "Organic Synthesis" during the second term and presents
the printed versions of Chemical Abstract and Beilstein and
the electronic version Crossfire/Beilstein.
In autumn and spring optional courses are run for staff and
students in the use of MEDLINE, IPA, and Analytical
Abstracts. Approximately 30 participants attend these cours-
es every term. As many services are now offered through
FARM-base - the Library’s OPAC – an introduction to FARM is
arranged for the staff every term.
A new initiative in September 2001 was participation in the
compulsory course "Social Pharmacy including Management
& Organisation" (5th term). It was arranged as a classroom
demonstration encouraging students to use electronic ser-
vices available on the school’s Intranet and on the Internet.
Continuing and postgraduate education: In January 2001,
the Department of Social Pharmacy arranged a postgraduate
course for student pharmacy advisors. The library contributed
a course entitled: Searching for information in the physical
and electronic library.
In connection with Danmarks
Farmaceutiske Selskabs Sektion for
Klinisk Farmacis (The Danish
Pharmaceutical Society – Section
for Clinical Pharmacy) course in
spring 2001, the research librarian
taught techniques for seeking infor-
mation on the Internet.
In summer 2001 the library par-
ticipated in a course for students
entitled "Specialist Education of
Pharmacy Practice".
Every January and October the
library offers a course to PhD stu-
dents: "Bibliographic Software.
Hands-on Use of the Reference
Manager." The course attracts
about 10 participants every time.
Alice Nørhede lectured at the
Royal School of Librarianship and Information Sciences for
fourth-term students as well as at two continuing education
courses in autumn 2000 and summer 2001. She also made a
presentation to the members of the Danish Librarians’ Group
for Medical Information in March 2001. All presentations fo-
cused on the theme: "Finding pharmaceutical information on
the Internet".
EVENTS, VISITS AND MEETINGS
November 2000 12 library students visited the Danish Phar-
maceutical Library. They attended a lecture held by Alice
Nørhede, presenting the library and its activities in the context
of the organisational, educational and economic conditions.
Later this winter, two library students visited the library and
interviewed the research librarian about the reference services.
Spring 2001 two colleagues from the library of Kann
Rasmussen (Velux) visited our library.
December 2001 two senior scientists from the Institute of
Pharmacology in Oslo visited the library to study the historical
collection of the library.
THE DANISH PHARMACEUTICAL L IBRARY
PAGE 105
January 2001 Alice Nørhede was twice a member on a
panel debating "The practical project" – part of the librarian
degree offered by The Royal School of Librarianship and
Information Science.
Alice Nørhede gave a lecture about the results of the li-
brary’s user survey DEF project called: "User satisfaction in the
electronic library" at the Nordic Summer School, The Royal
School of Librarianship and Information Sciences, July 2001.
Alice Nørhede made a presentation of the same project at
the official opening of the "DEF portal", September 2001.
MEMBERSHIP OF EXTERNAL ORGANISATIONS
AND COMMITTEES
Alice Nørhede
• Chairman of De Små Chefers Forum - an organisation of
approx. 200 smaller Danish research and special libraries
until August 2001. She is still a member of the Board.
• Appointed member of Biblioteksrådet (Library Council) an
advisory body for the Danish National Library Authority, until
August 2001.
• Second vice-president on the EAHIL Board (European
Association for Health Information and Libraries), until
January 2001.
• Member of The Danish Librarians' Group for Medical
Information.
• Member of a working group autumn 2000 at the Royal
School of Library and Information Services planning the end
of the Librarian degree programme as a practical project
analysing a concrete library-related issue.
• Appointed member to a committee by the Danish National
Authority until August 2001 dealing with superstructure and
information supply of the council libraries.
• Member from December 2001 of a working group dealing
with research library statistics.
Martin Weile
• Appointed member of the Danish Bibliographic Centre
Netpunkt working group 2001.
GRANTS
In the summer of 2001, the Library received a donation from
Apoteker J.B. Mikkelsens og hustru Kgl. translatrice
Gudrun Mikkelsens Farmaceutiske Fond. The donation
was used to buy software and books.
In the summer of 2001, the Library received a donation
from Apotekerfonden af 1991. The grant was used to buy
books for students taking the Specialist Education of
Pharmacy Practice.
See the Internet for more information about the library and
its activities.
The website of the Danish Pharmaceutical Library
www.dfh.dk/bibliotek
FARM (The Library's OPAC) http://dfb.dnlb.dk:8020/ALEPH
Danmarks Elektroniske Forskningsbibliotek www.deff.dk/
THE INFORMATION OFFICER
Jesper Munck, the information officer, is the editor of Plexus –
the official magazine issued by The Royal Danish School of
Pharmacy. Plexus was published in its current form for the
first time in 1999/2000 and is intended for employees and
students, as well as the pharmaceutical world outside the
School to some extent. Since its relaunch in 1999, both the
size and circulation of the publication have increased 20%. In
2000 Plexus began cooperating with De Danske Studieblade,
which handles advertising sales for seven Danish magazines
representing university institutions.
The information officer is a member of the editorial commit-
tee of Lægemiddelforsknings [Drug Research], a popular sci-
entific journal that publishes the results of the research con-
ducted by the Royal Danish School of Pharmacy and associ-
ated research centres.
The magazine is extremely popular with its the target group,
upper secondary chemistry and biology teachers, who re-
ceive the magazine free of charge every year.
A new recruitment website (www.dfh.dk/farmaceut) target-
ed at potential students was launched in February 2001. The
site is a team effort by the information officer along with MSc
Henrik Fylking Nielsen (Novo Nordisk) and Lærke Vester-
Andersen, study guide officer from the Course Administration.
In August 2001 a new webmaster, Henrik Korzen, joined
the School staff. He works together with the information offi-
cer to present the news and services, general content and
graphics for the School’s website.
Together with the registrar, study supervisors, PhD adminis-
tration and information committee, the information officer was
responsible for PR activities in conjunction with the School’s
Open House Day. The same team also put together the enrol-
ment materials – The pharmacist is the drug expert – and a
series of presentations focusing on the pharmacy degree pro-
gramme and its potential, and requirements for enrolment.
The information officer is the official contact person for the
press and other external bodies and he answers -or organis-
es responses to enquiries to the School.
MEMBERSHIP OF EXTERNAL ORGANISATIONS
AND COMMITTEES
Jesper Munck is a:
• Member of EUPRIO (European Universities Public Relations
and Information Officers Association)
ANNUAL REPORT 2000–2001
PAGE 106
• Member of NUAS-Informatörsektion (NUAS: The Nordic
Universities’ information co-operation)
• Member of the Danish universities’ information employees
group
• Member of Danske Videnskabsjournalister (Danish
Scientific Journalists)
• Specialist contact person for Aktuel Naturvidenskab
(Modern Science)
THE DANISH PHARMACEUTICAL L IBRARY
PAGE 107
Well aware of the increased competition for potential students, the Royal Danish School of Pharmacy advertised in Danish me-
dia twice during 2001. In March the School released a poster, The pharmacist is the drug expert, and followed up a month later
with an advertisement in the magazine Chili headlined: Get high on pharmacy – it’s legal. In both layout and content, the adver-
tisement was a response to an article run the previous month by the same magazine entitled: Get stoned at the pharmacy – it’s
legal. The School’s advertisement was edited slightly to become the flyer for the School’s annual Open House Day. The flyer was
also handed out to upper secondary schools in the autumn of 2001 at study orientation meetings called STORM meetings.
Advertising
Publications
DEPARTMENT OF ANALYTICAL
AND PHARMACEUTICAL CHEMISTRY
Andersen HR, Wollenberger L, Halling-Sørensen B, Kusk KO.Development of copopod nauplii to copepodites - A parameter forchronic toxicity including endocrine disruption. Environ Tox and Chem2001;20:2821-2829.
Bendahl L, Gammelgaard B, Jøns O, Farver O, Hansen SH.Interfacing capillary electrophoresis with inductively coupled plasmamass spectrometry by direct injection nebulization for selenium specia-tion. J Anal At Spectrom. 2001;16:38-42.
Bendahl L, Hansen SH, Gammelgaard B. Capillaries modified bynon-covalent anionic polymer adsorption for capillary zone elec-trophoresis, micellar electrokinetic capillary chromatography and capil-lary electrophoresis mass spectrometry. Electrophoresis2001;22:2565-73.
Corcoran O, Mortensen RW, Hansen SH, Troke J, Nicholson JK.HPLC/1H NMR spectroscopic studies of the reactive -1-O-acyl isomerformed during acyl migration of S-naproxen-1-O-acyl glucuronide.Chem Res Toxicol 2001;14:1363-1370.
Daykin CA, Corcoran O, Hansen SH, Bjørnsdottir I, Cornett C,Connor SC, Lindon JC, Nicholson JK. Application of directly-cou-pled HPLC-NMR to separation and characterisation of lipoproteinsfrom human serum. Anal Chem 2001;73:1084-1090.
Farver O, Zhang J, Chi O, Pecht I, Ulstrup J. Deuterium IsotopeEffect on the Intramolecular Electron Transfer in Pseudomonas aerugi-nosa Azurin, Proc Natl Acad Sci 2001;98:4426-4430.
Farver O, Kroneck PMH, Zumft WG, Pecht I. Intra-protein electrontransfer processes - from model proteins to enzymatic reaction cycles.J Inorg Biochem 2001;86:84-86.
Gabel-Jensen C, Hansen SH, Pedersen-Bjergaard S. Separation ofneutral compounds by microemulsion electrokinetic chromatography.Fundamental studies on selectivity. Electrophoresis 2001;22:1330-1336.
Gammelgaard B, Bendahl L, Jøns O. Selenium speciation in humanurine. Plasma Source Mass Spectrometry: The New Millenium2001;401-411.
Gammelgaard B, Jøns O, Bendahl L. Selenium speciation in pre-treated human urine by ion-exchange chromatography and ICP-MSdetection. J Anal At Spectrom 2001;16:339-344.
Guardo AD, Calamari D, Benfenati E, Halling-Sørensen B, ZucattoE, Fanelli R. Pharmaceuticals as Environmental Contaminats:
Modelling Distribution of fate. Pharmaceuticals in the environment -Sources, fate, effects and risks 2001;91-102.
Halling-Sørensen B, Holten Lützhøft HC, Andersen HR, Ingerslev F.Environmental Risk Assessment of Antibiotics; Comparison ofMecillinam, Trimethoprim and Ciprofloxacin. J AntimicrobialChemotherapy 2000;46:53-58.
Halling-Sørensen B. Inhibition of aerobic growth and nitrification ofbacteria in sewage sludge by antibacterial agents Arch EnvironContam Toxicol 2001;40:451-460.
Halling-Sørensen B, Jensen J, Tjørnelund J, Montfors MHMM.Worst-case estimations of predicted environmental soil concentrations(PEC) of selected veterinary antibiotics and residues in DanishAgriculture. Pharmaceuticals in the environment - Sources, fate,effects and risks 2001;143-156.
Halling-Sørensen B, Sengeløv G, Tjørnelund J. Toxicity ofTetracyclines and Tetracycline degradation products to environmentalrelevant bacteria including selected Tetracycline resistant bacteria.Arch Environ Contam Toxicol (in press).
Hansen HH, Hansen SH, Schousboe A, Hansen HS. Determinationof an anandamide precursor (N-acylethanolamine phospholipid) andother N-acylethanolamine phospholipids following sodium azide-in-duced neurotoxicity in cortical neurons. J Neurochem 2000;75:861-871.
Hansen HH, Ikonomidou C, Bittigau P, Hansen SH, Hansen HS.Accumulation of the anandamide precursor and other N-acylethanolamine phospholipids in infant rat models of in vivo necroticand apoptotic neuronal death. J Neurochem 2001;76:39-46.
Hansen SH, Bjørnsdottir I, Tjørnelund J. Nonaqueous CapillaryElectrophoresis. Encyclopedia of Separation Science 2000;1293-1300.
Hansen SH, Gabel-Jensen C, Pedersen-Bjergaard. Comparison ofmicroemulsion electrokinetic chromatography and solvent modified mi-cellar electrokinetic chromatography. J Sep Sci 2001;24:643-650.
Hansen SH, Gabel-Jensen C, El-Sherbiny DTM, Pedersen-Bjergaard S. Microemulsion electrokinetic chromatography - orsolvent-modified micellar electrokinetic chromatography? TRAC2001;20:614-619.
Jensen AG, Hansen SH, Nielsen EØ. Adhyperforin as a contributorto the effect of Hypericum perforatum L. in biochemical models of an-tipressant activity. Life Sciences 2001;68:1593-1605.
Jensen AG, Cornett C, Gudiksen L, Hansen SH. Characterization ofextracts of Hypericum perforatum L. Using an on-line HPLC system withUV/VIS and fluorescence detection before as well as after photochemi-cal conversion of the effluent. Phytochemical Analysis 2000;11:387-394.
ANNUAL REPORT 2000–2001
PAGE 108
Jensen CG, Hansen SH, Pedersen-Bjergaard S. Separation of neutralcompounds by microemulsion electrokinetic chromatography.Fundamental studies on selectivity. Electrophoresis 2001;22:1330-1336.
Jørgensen SE. Application of exergy and specific exergy as ecologicalindicators of coastal areas. Aquatic Ecosystem Health andManagement 2000;3:419-430.
Jørgensen SE, Trepel M, Davidson T. Quantitative simulation of bio-chemical processes in petlands as a tool to define sustainable use?Suo 2000;3:83-93.
Jørgensen SE. Toward a Consistent Pattern of Ecosystem Theories.The Scientific World 2001;1:71-75.
Jørgensen SE. The thermodynamic Concept Exergy.Thermodynamics and Ecological Modelling 2001;153-164.
Jørgensen SE. A tentative Fourth Law of Thermodynamics.Thermodynamics and Ecological Modelling 2001;302-348.
Jørgensen SE, Marques JC. Thermodynamics and ecosystem theo-ry, case studies from hydrobiology. Hydrobiologia 2001;445:1-10.
Jørgensen SE. Exergy of an isolated living system may increase.Advances in Energy Studies 2001;573-580.
Jørgensen SE. Parameter estimation and calibration by use of exergy.Ecological Modelling 2001;146:299-302.
Jørgensen SE. Recent Developments in System Ecology. IntegrativeSystem Approaches to Natural and Social Dynamics 2001;155-170.
Larsen SW, Thomsen AE, Rinvar E, Friis GJ, Larsen C. Effect ofdrug lipophilicity on in vitro release rate from oil vehicles using nicotinicacid esters as model prodrug derivatives. Int J Pharm 2001;216:83-93.
Larsen DB, Fredholt K, Larsen C. Addition of hydrogen bond donat-ing excipients to oil solution: effect on in vitro release rate and viscosi-ty. Eur J Pharm Sci 2001;13:403-410.
Larsen SW, Rinvar E, Svendsen O, Lykkesfeldt J, Friis GJ, LarsenC. Determination of the disappearance rate of iodine-125 labelled oilsfrom the injection site after intramuscular and subcutaneous adminis-tration to pigs. Int J Pharm 2001;230,67-75.
Loke ML, Tjørnelund J, Halling-Sørensen B. Determination of thedistribution coefficient (log kd) of oxytetracycline, tylosin, olaquindoxand metronidazole in manure. Chemosphere (accepted).
Mortensen RW, Corcoran O, Cornett C, Sidelmann UG, Throke J,Lindon JC, Nicholson JK, Hansen SH. LC-1H NMR used for deter-mination of the elution order of S-naproxen glucuronide isomers in twoisocratic reversed-phase LC-systems. J Pharm Biomed Anal2001;24:477-485.
Mortensen RW, Corcoran O, Cornett C, Sidelmann UG, Lindon JC,Nicholson JK, Hansen SH. S-naproxen-1-O-acyl glucuronide degra-dation kinetic studies by stopped-flow HPLC-1H NMR and HPLC-UV.Drug Metabolism and Disposition 2001;29:375-380.
Ray S, Berec L, Straskraba M, Jørgensen SE. Optimization of exer-gy and implication of body sizes of phytoplankton and zooplankton inan aquatic ecosystem model. Ecological Modelling volume2001;140:219-234.
Pedersen-Bjergaard S, Jensen CG, Hansen SH. Selectivity in mi-croemulsion electrokinetic chromatography. J Chromatogr A2000;897:375-381.
Strømgaard K, Bjørnsdottir I, Andersen K, Brierley MJ, Rizoli S,Eldursi N, Mellor IR, Usherwood PNR, Hansen SH, Krogsgaard-Larsen P, Jaroszewski J. Solid phase synthesis and biological evalu-ation of enantiomerically pure wasp toxin analogues PhTX-343 andPhTX-12. Chirality 2000;12:93-102.
Wang J, Hansen EH, Gammelgaard B. Flow injection on-line dilutionfor multi-element determination in human urine with detection by in-ductively coupled plasma mass spectrometry. Talanta 2001;55:117-126.
PHD THESES
Gyldenkærne S. Risk Assessment of Pesticides in Agricultural Fieldswith Special Emphasis on Carabids and Staphylinids. The RoyalDanish School of Pharmacy, 2000.
Jensen AG. Quality Assessment of Herbal Remedies. Focus onPhytopharmaceuticals Containing Hypericum perforatum L. and Ginkobiloba L. Department of Analytical and Pharmaceutical Chemistry, TheRoyal Danish School of Pharmacy, 2001.
Jensen MS. Cyanide Toxicology – Insights into Mechanisms of Actionand Antidotal Strategies. Department of Analytical and PharmaceuticalChemistry, The Royal Danish School of Pharmacy, 2000.
Larsen DB. Parenteral depot formulations - pharmaceutical chemicalcharacterization of oil solutions. Royal Danish School of Pharmacy,Dept. of Analytical and Pharmaceutical Chemistry, 2001.
Lützhøft H-CH. Environmental Risk Assessment of Antimicrobials.Royal Danish School of Pharmacy, Department of Analytical andPharmaceutical Chemistry, 2000.
Kayombo S. Development of a Holistic Model for the design ofFacultative Waste Stabilisation Ponds in Tropical Climate. Section ofEnvironmental Chemistry, Department of Analytical and PharmaceuticalChemistry, Royal Danish School of Pharmacy, 2001.
Mortensen RW. Reactive Drug Metabolites: Investigations of R- andS-naproxen-1-0-acyl glucuronide degradation using enzymes, HPLCand NMR. Department of Analytical and Pharmaceutical Chemistry,Royal Danish School of Pharmacy, 2000.
Sidenius U. Purification and analysis of selenoprotein P from humanplasma. The Royal Danish School of Pharmacy, Dept. of Analytical andPharmaceutical Chemistry, 2000.
OTHER PUBLICATIONS
Bendahl L, Gammelgaard B, Jøns O, Farver O, Hansen SH.Højfølsomme mikroteknikker til analyse af blod og urin. [Sensitive mi-cro techniques for analysis of blood and urine] Lægemiddelforskning2001;36-37.
Halling-Sørensen B. Miljøforurening fra rester af antibiotika i organiskaffald og husdyrgødning. [Environmental pollution from residue of an-tibiotic in organic waste and domestic animal manure] Miljøforskning2001;49.
Hansen HH, Hansen SH, Hansen HS. Hjernens cannabis-lignendestoffer modvirker hjernedød. [The cannabis like drugs of the brain pre-vent brain death] Lægemiddelforskning 2000;26-27.
Hansen SH. Naturlægemidler og mineralpræparater. Sammenhængmellem indhold og virkning? [Natural medicine and mineral prepara-tions. A connection between content and effect?] Farmaci2000;107:22-26.
Hansen SH, Jensen AG, Cornett C. PERIKON – Den „grønne“lykkepille. [PERIKON – the ”green” prozac] Farmaci 2001;108:26-27.
Jensen AG, Cornett C, Hansen SH. Naturlægemidler.[Naturalmedicine] Dansk Kemi 2001;82:16-20.
Jørgensen SE. Milan Straskraba, editorial Ecological Modelling2001;140:193-194.
PUBLICATIONS
PAGE 109
Jørgensen SE. Foreword to the book “Pharmaceuticals in the environ-ment. Sources, Fate, Effects and Risks” edited by Kalus Kümmerer2001.
Jørgensen SE, Bendoricchio G. Fundamentals of EcologicalModelling 3. Edition. 2001.
Olsen J, Bjørnsdottir I, Tjørnelund J, Hansen SH. På sporet afbivirkningen. [Tracking down the side effect] Lægemiddelforskning2000;10-11.
DEPARTMENT OF MEDICINAL CHEMISTRY
Andersen L, Clausen V, Oketch-Rabah HA, Lechtenberg M,Adsersen A, Nahrstedt A, Jaroszewski JW. Gynocardin andcyclopentenylglycine in Rawsonia lucida. Biochem Syst Ecol29;2001:219-222.
Andersen L, Nielsen B, Jaroszewski JW. Synthesis of epimers of L-cyclopentenylglycine using enzymatic resolution. Chirality12;2000:665-669.
Bang-Andersen B, Ahmadian H, Lenz SM, Stensbøl TB, MadsenU, Bøgesø KP, Krogsgaard-Larsen P. Structural determinants ofAMPA agonist activity in anlogues of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid: Synthesis and pharmacology. J Med Chem43;2000:4910-4918.
Banke TG, Greenwood JR, Christensen JK, Liljefors T, TraynelisSF, Schousboe A, Pickering DS. Identification of amino acid residuesin GluR1 responsible for ligand binding and desensitization. J Neurosci21;2001:3052-3062.
Begtrup M. Small-scale filtration using a modified plastic syringe. JChem Ed 78;2001:543.
Boström J, Gundertofte K, Liljefors T. A pharmacophore model fordopamine D4 receptor antagonists. J Comput-Aided Mol Des14;2000:769-786.
Bräuner-Osborne H, Jensen AA, Sheppard PO, Brodin B,Krogsgaard-Larsen P, O’Hara P. Cloning and characterization of ahuman orphan family C G-protein coupled receptor GPRC5D. BiochimBiophys Acta 1518;2001:237-248.
Bräuner-Osborne H, Nielsen MB, Nielsen B, Krogsgaard-Larsen P,Johansen TN. A new structural class of subtype-selective inhibitor ofcloned excitatory amino acid transporter, EAAT2. Eur J Pharmacol406;2000:41-44.
Breu J, Domel H, Norrby P-O. Chiral recognition among trisdiimine –metal complexes, 7. Racemic compound formation versus conglomer-ate formation with [M(bpy)3](PF6)2 (M = Ni, Zn, Ru): Lattice energy min-imisations and implications for structure prediction. Eur J Inorg Chem2000:2409-2419.
Bunch L, Johansen TH, Bräuner-Osborne H, Stensbøl TB,Johansen TN, Krogsgaard-Larsen P, Madsen U. Synthesis and re-ceptor binding affinity of new selective GluR5 ligands. Bioorg MedChem 9;2001:875-879.
Bunch L, Norrby P-O, Frydenvang K, Krogsgaard-Larsen P,Madsen U. Unprecedented migration of N-alkoxycarbonyl groups inprotected pyroglutaminol. Org Lett 3;2001:433-435.
Campiani G, Morelli E, Nacci V, Fattorusso C, Ramunno A,Novellino E, Greenwood J, Liljefors T, Griffiths R, Sinclair C,Reavy H, Kristensen AS, Pickering DS, Schousboe A, Cagnotto A,Fumagalli E, Mennini T. Characterization of the 1H-cyclopentapyrimi-dine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, andsubtype-selective AMPA receptor full agonist with partial desensitiza-tion properties. J Med Chem 44;2001:4501-4504.
Chen M, Zhai L, Christensen SB, Theander TG, Kharazmi A.Inhibition of Furamate reductase in Leishmania major and L. donovaniby chalcones. Antimicrob Agents Chemother 45;2001:2023-2029.
Christensen J, Jaroszewski JW. Natural glycosides containing al-lopyranose from the passion fruit plant and circular dichroism of ben-zaldehyde cyanohydrin glycosides. Org Lett 3;2001:2193-2195.
Christensen SB, Kharazmi A. Antimalarial Natural Products (chapter9). In: Bioactive Compounds from Natural Sources, editor Tringali C.London: Taylor and Francis, 2001.
Clausen V, Wellendorph P, Ekpe P, Jaroszewski JW. Tetraphyllin B,volkenin and cyclopentenyl-glycine in Androsiphonia adenostegia.Biochem Syst Ecol 29;2001:317-319.
Ebert B, Mortensen M, Thompson SA, Kehler J, Wafford KA,Krogsgaard-Larsen P. Bioisosteric determinants for subtype selectivi-ty of ligands for heteromeric GABAA receptors. Bioorg Med Chem Lett11;2001:1573-1577.
Eldrup AB, Nielsen BB, Haaima G, Rasmussen H, Kastrup JS,Christensen C, Nielsen PE. 1,8-Naphthyridin-2(1H)-ones. Novel bi-and tricyclic analogues of thymine in peptide nucleic acids (PNAs). EurJ Org Chem 2001;1781-1790.
Eriksen BL, Vedsø P, Begtrup M. Synthesis of 4- and 5- substituted1-hydroxyimidazoles through directed lithiation and metal-halogen ex-change. J Org Chem 66;2001:8344-8348.
Eskildsen J, Vedsø P, Begtrup M. Synthesis of 2-alkylpyrazole-1-ox-ides: A facile access to 1-alkyl-5-halopyrazoles. Synthesis 72001;1053-1056.
Friedrichsen GM, Jakobsen P, Taub M, Begtrup M. Application ofenzymatically stable dipeptides for enhancement of intestinal perme-ability. Synthesis and in vitro evaluation of dipeptid-coupled com-pounds. Bioorg Med Chem 9;2001:2625-2632.
Friedrichsen GM, Nielsen CU, Steffansen B, Begtrup M. Modelprodrugs designed for the intestinal peptide transporter. A syntheticapproach for coupling of hydroxy-containing compounds to dipep-tides. Eur J Pharm Sci 14;2001:13-19.
Frølund B, Tagmose L, Liljefors T, Stensbøl TB, Engblom C,Kristiansen U, Krogsgaard-Larsen P. A novel class of potent 3-isoxazolol GABAA antagonists: Design, synthesis and pharmacology. J Med Chem 43;2000:4930-4933.
Garibay P, Vedsø P, Begtrup M, Hoeg-Jensen T. Solid-phase direct-ed ortho-lithiation and the preparation of a phthalide library. J CombChem 3;2001:332-340.
Havez S, Begtrup M, Vedsø P, Andersen K, Ruhland T.Palladium(0)-catalyzed arylation of resin-bound imidazol-2-ylzinc chlo-rides. Synthesis 2001:909-913.
Høgedal BD, Mølgaard P. HPLC analysis of the seasonal and diurnalvariation of iridoids in cultivars of Antirrhinum majus. Biochem SystEcol 28;2000:949-962.
Jakobsen CM, Denmeade SR, Isaacs JT, Gady A, Olsen CE,Christensen, SB. Design, synthesis, and pharmacological evaluationof thapsigargin analogues for targeting apostosis to prostatic cancercells. J Med Chem 44;2001:4696-4703.
Jakobsen TH, Marcussen HV, Adsersen A, Strasberg D, Smitt UW,Jaroszewski JW. 3-Methoxyflavones and a novel coumarin fromPsiadia dentata. Biochem Syst Ecol 29;2001:963-965.
Jensen J, Skjærbæk N, Vedsø P. Preparation of 2- and 5-aryl substi-tuted thiazoles via Palladium-catalyzed Negishi cross-coupling.Synthesis 2001;128-134.
ANNUAL REPORT 2000–2001
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Jensen AA, Madsen BE, Krogsgaard-Larsen P, Bräuner-Osborne H.Pharmacological characterization of homobaclofen on wild type andmutant GABAB1b receptors coexpressed with the GABAB2 receptor.Eur J Pharmacol 417;2001:177-180.
Jensen AA, Sheppard PO, O'Hara PJ, Krogsgaard-Larsen P,Bräuner-Osborne H. The role of Arg78 in the metabotropic glutamatereceptor mGlu1 for agonist and selectivity. Eur J Pharmacol2000;397:247-253
Jensen AA, Sheppard PO, Jensen LB, O’Hara PJ, Bräuner-Osborne H. Construction of a high affinity zinc binding site in themetabotropic glutamate receptor mGluR1. J Biol Chem276;2001:10110-10118.
Jensen AA, Spalding TA, Burstein ES, Sheppard PO, O’Hara PJ,Brann MR, Krogsgaard-Larsen P, Bräuner-Osborne H. Functionalimportance of the Ala116-Pro136 region in the calcium-sensing receptor.J Biol Chem 275;2000:29547-29555.
Jensen KP, Sauer SPA, Liljefors T, Norrby P-O. Theoretical investi-gation of steric and electronic effects in coenzyme B12 models.Organometallics 20;2001:550-556.
Johansen TN, Stensbøl TB, Nielsen B, Vogensen SB, FrydenvangK, Sløk FA, Bräuner-Osborne H, Madsen U, Krogsgaard-Larsen P.Resolution, configurational assignment, and enantiopharmacology atglutamate receptors of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) and demethyl-ACPA. Chirality13;2001:523-532.
Kastrup JS, Linde V, Pedersen AK, Stoffer B, Iversen LF, LarsenIK, Rasmussen PB, Flodgaard HJ, Bjørn SE. Two mutants of humanheparin binding protein (CAP37): Toward an understanding of the na-ture of lipid A/LPS and BPTI binding. Proteins: Struct Funct Genet42;2001:442-451.
Krebs FC, Jørgensen M, Lebech B, Frydenvang K. A perdeuteratedcryoprotectant for neutron studies and a demonstration of its use forneutron powder diffraction on L-(—)-ephedrine hemihydrate. J ApplCryst 34;2001:203-207.
Kreilgaard M, Pedersen EJ, Jaroszewski JW. NMR characterisationand transdermal drug delivery potential of microemulsion systems. JControlled Release 69;2000:421-433.
Kristensen J, Lysén M, Vedsø P, Begtrup M. Synthesis of ortho sub-stituted arylboronic esters by in situ trapping of unstable lithio interme-diates. Org Lett 3;2001:1435-1437.
Krogsgaard-Larsen P, Frølund B, Frydenvang K. GABA uptake in-hibitors. Design, molecular pharmacology and therapeutic aspects.Curr Pharm Des 6;2000:1193-1209.
Kromann H, Sløk FA, Johansen TN, Krogsgaard-Larsen P. A con-venient synthesis of 4-substituted 3-ethoxy-5-methylisoxazoles by pal-ladium-catalyzed coupling reactions. Tetrahedron 57;2001:2195-2201.
Larsen ST, Hansen JS, Thygesen P, Begtrup M, Poulsen OM,Nielsen GD. Adjuvant and immuno-suppressive effect of six monoph-thalates in a subcutaneous injection model with BALB/c mice.Toxicology 169;2001:37-51.
Larsen TO, Frydenvang K, Frisvad JC. UV-guided screening of ben-zodiazepine producing species in Penicillium. Biochem Syst Ecol28;2000:881-886.
Mader MM, Norrby P-O. Quantum chemical investigation of mecha-nism of silane oxidation. J Am Chem Soc 123;2001:1970-1976.
Madsen U, Bräuner-Osborne H, Frydenvang K, Hvene L,Johansen TN, Nielsen B, Sánchez C, Stensbøl TB, Bischoff F,Krogsgaard-Larsen P. Synthesis and pharmacology of 3-isoxazololamino acids as selective antagonists at group I metabotropic glutamicacid receptors. J Med Chem 44;2001:1051-1059.
Madsen U, Johansen TN, Stensbøl TB, Krogsgaard-Larsen P.Pharmacology of AMPA/kainate receptors. In: Glutamate and GABAreceptors and transporters. Eds: Egebjerg J, Schousboe A,Krogsgaard-Larsen P. London: Taylor and Francis Books Ltd 2001;pp. 99-118.
Madsen U, Stensbøl TB, Krogsgaard-Larsen P. Inhibitors of AMPAand kainate receptors. Curr Med Chem 8;2001:1291-1301.
Mølgaard P, Chihaka A, Lemmich E, Furu P, Windberg C, IngerslevF, Halling-Sørensen B. Biodegradability of the Molluscicidal Saponinsof Phytolacca dodecandra. Regul Toxicol Pharmacol 32;2000:248-255.
Mølgaard P, Ndamba J, Lemmich E, Chihaka A, Furu P. PhytolaccaDodecandra used as a molluscicide in Zimbabwe. In: Timberlake J &Kativu S (Eds), African Plants: Biodiversity, Taxonomy and Uses.Ethnobotany and Uses of African Plants Symposium Poster Abstracts.Royal Botanic Gardens, Kew, 1999:507.
Mølgaard P, Nielsen SB, Rasmussen DE, Drummond RB, MakazaN, Adreassen J. Anthelmintic screening of Zimbabwean plants tradi-tionally used against schistosomiasis. J Ethnopharmacol 2001;74:257-264
Nielsen PA, Jaroszewski JW, Norrby P-O, Liljefors T. An NMR andab initio quantum chemical study of acid-base equilibria for conforma-tionally constrained acidic �-amino acids in aqueous solution. J AmChem Soc 123;2001:2003-2006.
Nielsen PA, Liljefors T. Conformational analysis of kainate in aqueoussolution in relation to its binding to AMPA and kainic acid receptors. JComput-Aided Mol Des 15;2001:753-763.
Norrby P-O, Brandt P. Deriving force field parameters for coordinationcomplexes. Coord Chem Rev 212;2001:79109.
Olafsdottir ES, Omarsdottir S, Jaroszewski JW. Constituents ofthree Icelandic Alchemilla species. Biochem Syst Ecol 29;2001:959-962.
Pawlas J, Greenwood J, Vedsø P, Liljefors T, Jakobsen P,Huusfeldt PO, Begtrup M. Halogenation of pyrazoloquinolines andpyrazoloisoquinolines. Thereoretical analysis of the regioreactivity andcross-coupling of 3-halogen derivatives. J Chem Soc Perkin Trans I2001:861-866.
Pawlas J, Vedsø P, Jakobsen P, Huusfeldt PO, Begtrup M.Synthesis of 1-hydroxy-substituted pyrazolo[3,4-c]- and pyrazolo[4,3-c]quinolines and isoquinolines from 4- and 5-aryl-substituted 1-benzy-loxypyrazoles. J Org Chem 65;2000:9001-9006.
Rasmussen HB, Christensen SB, Kvist LP, Kharazmi A, HuansiAG. Absolute configuration and antiprotozoal activity of minquartynoicacid. J Nat Prod 63;2000:1295-1296.
Rasmussen T, Norrby P-O. Characterization of new six-memberedtransition states of the amino-alcohol promoted addition of dialkyl zincto aldehydes. J Am Chem Soc 123;2001:2464-2465.
Rist Ø, Begtrup M. Synthesis of a new analogue of BINOL based ona homodimer of substituted 1-hydroxypyrazole. J Chem Soc PerkinTrans I 2000:1566-1568.
Rønsted N, Göbel E, Franzyk H, Jensen SR, Olsen CE.Chemotaxonomy of Plantago. Iridoid glucosides and caffeoylphenylethanoid glycosides. Phytochemistry 55;2000:337-348.
Sairafianpour M, Christensen J, Stærk D, Budnik BA, Kharazmi A,Bagherzadeh K, Jaroszewski JW. Leishmanicidal, antiplasmodial,and cytotoxic activity of novel diterpenoid 1,2-quinones from Perovskiaabrotanoides: New source of tanshinones. J Nat Prod 64;2001:1398-1403.
PUBLICATIONS
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Sandager L, Stymne S. Characterization of enzymes determining fat-ty acid chain lenght in developing seeds of Limnanthes douglasii. JPlant Phys 156;2000:617-622.
Simonsen HT, Nordskjold JB, Smitt UW, Nyman U, PushpangadanP, Joshi P, Varughese G. In vitro screening of Indian medicinal plantsfor antiplasmodial activy. J Ethnopharmacol 74;2001,195-204.
Sløk FA, Bräuner-Osborne H, Stensbøl TB, Johansen TN, Ebert B,Mortensen M, Nielsen B, Madsen U, Brehm L, Falch E,Krogsgaard-Larsen P. Structural and stereochemical requirements foractivation and blockade of excitatory amino acid receptors.
Smith L, Andersen KB, Hovgaard L, Jaroszewski JW. Rational se-lection of antisense oligonucleotide sequences. Eur J Pharm Sci11;2000:191-198.
Stensbøl TB, Jensen HS, Nielsen B, Johansen TN, Egebjerg J,Frydenvang K, Krogsgaard-Larsen P. Stereochemistry and molecularpharmacology of (S)-thio-ATPA, a new potent and selective GluR5 ag-onist. Eur J Pharmacol 411;2001:245-253.
Strømgaard K, Andersen K, Krogsgaard-Larsen P, JaroszewskiJW. Recent advances in the medicinal chemistry of polyamine toxins.Mini Rev Med Chem 1;2001:317-338.
Strømgaard K, Andersen K, Ruhland T, Krogsgaard-Larsen P,Jaroszewski JW. A versatile method for solid-phase synthesis ofpolyamines: Neuroactive polyamine toxins as example. Synthesis 62001:877-884.
Strømgaard K, Brier TJ, Andersen K, Mellor IR, Saghyan A,Tikhonov D, Usherwood PNR, Krogsgaard-Larsen P, JaroszewskiJW. Solid-phase synthesis and biological evaluation of a combinatoriallibrary of philanthotoxin analogues. J Med Chem 43;2000:4526-4533.
Stærk D, Christensen J, Lemmich E, Duus JØ, Olsen CE,Jaroszewski JW. Cytotoxic activity of some phenanthroindolizidine N-oxide alkaloids from Cynanchum vincetoxicum. J Nat Prod63;2000:1584-1586.
Stærk D, Norrby P-O, Jaroszewski JW. Conformational analysis ofindole alkaloids corynantheine and dihydrocorynantheine by dynamic1H NMR spectroscopy and computational methods: Steric effects ofethyl vs vinyl group. J Org Chem 66;2001:2217-2221.
Sørensen US, Falch E, Stensbøl TB, Jaroszewski JW, Madsen U,Krogsgaard-Larsen P. Structural determinants for AMPA agonist ac-tivity of aryl or heteroaryl subtstituted AMPA analogues. Synthesis andpharmacology. Arch Pharm Pharm Med Chem 334;2001:62-68.
Sørensen US, Krogsgaard-Larsen P. Synthesis and synthetic utilityof 3-isoxazolols. Org Prep Proced Int 33;2001:515-564.
Terp GE, Johansen BN, Christensen IT, Jørgensen FS. A new con-cept for multidimensional selection of ligand conformations(Multiselect) and multidimensional scoring (Multiscore) of protein –ligang binding affinities. J Med Chem 44;2001:2333-2343.
Tønder JE, Olesen PH, Hansen JB, Begtrup M, Pettersson I. Animproved nicotinic pharmacophore and a stereoselective CoMFA-mod-el for nicotinic agonists acting at the central nicotinic acetylcholine re-ceptors labelled by [3H]-N-methylcarbamylcholine. J Comput-AidedMol Des 15;2001:247-258.
Vogensen SB, Jensen HS, Stensbøl TB, Frydenvang K, Bang-Andersen B, Johansen TN, Egebjerg J, Krogsgaard-Larsen P.Resolution, configurational assignment, and enantiopharmacology of2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propi-onic acid, a potent GluR3- and GluR4-preferring AMPA receptor ago-nist. Chirality 12;2000:705-713.
Wellendorp P, Clausen V, Jørgensen LB, Jaroszewski JW.Cyclopentanoids of Mathurina penduliflora. Biochem Syst Ecol29;2001:649-651.
PHD THESES
Buchardt J. A solid phase combinatorial approach to phosphinic pep-tide inhibitors of matrix metalloproteinases. Carlsberg Laboratory andRoyal Danish School of Pharmacy, 2000.
Friedrichsen GM. Peptide-coupled compounds targeted for theoligopeptide transporter: Synthesis and biological evaluation. RoyalDanish School of Pharmacy, 2001.
Garibay P. The combinatorial synthesis of possible insulin mimetics.Royal Danish School of Pharmacy, 2000.
Jakobsen CM. Design, synthesis, and pharmacological evaluation ofThapsigargin analogues and prodrugs for targeting apoptosis to pro-static cancer cells. Royal Danish School of Pharmacy, 2001.
Jensen AA. Molecular pharmacology of family C G G-protein coupledreceptors. Royal Danish School of Pharmacy, 2001.
Kromann H. Glutamate receptor-ligands: Synthesis and pharmacolog-ical characterization. Royal Danish School of Pharmacy, 2000.
Nielsen PA. Strongly polar molecules in aqueous solution studied byNMR and computational chemistry. Royal Danish School of Pharmacy,2000.
Pawlas JI. Construction and functionalization of annelated 1-hydrox-ypyrazoles. II Nickel-catalyzed hydroamination of 1,3-dienes using alkylamines. Royal Danish School of Pharmacy, 2001.
Rasmussen T. Molecular modeling of asymmetric catalysts. RoyalDanish School of Pharmacy, 2001.
Sams AG. Solid phase aldol and Diels-Alder reactions in the formationof novel peptide isosters as putative protease inhibitors. Royal DanishSchool of Pharmacy, 2000.
Sandager L. Genes and enzymes involved in the biosynthesis of tria-cylglycerol in plants and yeast. Swedish University of AgriculturalSciences, Alnarp and Royal Danish School of Pharmacy, 2001.
Terp GE. Molecular modeling of matrix metalloproteinases and their in-hibitors: A new concept for ligand selection and prediction of bindingaffinities. Royal Danish School of Pharmacy, 2001.
Willert M. A combinatorial library approach to the identification of pro-tease substrates and inhibitors. Carlsberg Laboratory and RoyalDanish School of Pharmacy, 2001.
OTHER PUBLICATIONS
Christensen J, Stærk D, Ziegler HL, Sairafianpour M, Jaroszewski,JW. Forbedret test af nye lægemidler mod malaria [Improved assay fornew antimalarial drugs]. Lægemiddelforskning 2001;8-9.
Clausen RP, Greenwood J, Larsson OM, Krogsgaard-Larsen P. Etbud på fremtidens lægemidler mod epilepsi [Future anti-epilepticdrugs]. Lægemiddelforskning 2001;20-21.
Frølund B, Kristiansen U, Stensbøl TB, Krogsgaard-Larsen P. Nynøgle til behandling af skizofreni? [A new strategy for treatment ofschizophrenia?]. Lægemiddelforskning 2000;24-25.
Hogner A, Lunn M-L, Kastrup JS, Larsen IK, Liljefors T, EgebjergJ. Design af lægemidler mod neurodegenerative sygdomme [Structurebased design of drugs against neurodegenerative diseases].Lægemiddelforskning 2000;32-33.
Høst J, Jørgensen FS, Christensen IT, Hovgaard L, Frøkjær S.Computeren er medicinalindustriens krystalkugle.Lægemiddelforskning 2001;28-29.
ANNUAL REPORT 2000–2001
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Jensen AA, Bräuner-Osborne H. Øget forståelse af vigtig receptor ihjernen [Increased understanding of important receptor in the brain].Lægemiddelforskning 2000;28-29.
Jørgensen FS, Kristensen JB, Christensen IT. E-screening aflægemidler [e-Screening of Drugs]. Lægemiddelforskning 2001;30-31.
Krogsgaard-Larsen P, Brehm L. Fra svampegift til potentieltlægemiddel med ny virkning [From mushroom toxin to potential drugwith new clinical profile]. Lægemiddelforskning 2001;2-5.
Madsen U, Stensbøl TB, Bräuner-Osborne H, Sánchez C. Frakrampefremkaldende til krampestillede effekt [From convulsive to anti-convulsive activity]. Lægemiddelforskning 2001;18-19.
Mortensen M, Kehler J, Krogsgaard-Larsen P, Ebert, B. Nytlægemiddel forbedrer søvnen [New drug improves sleep pattern].Lægemiddelforskning 2001;6-7.
Mølgaard P, Cornett C. Rationel omgang med naturlægemidler [A ra-tional approach to herbal medicine]. Dansk Kemi 2001;82.
Mølgaard P, Johnsen S, Christensen P, Cornett C. Kemisk og biolo-gisk evaluering af ekstrakter og stoffer fra Rød Solhat [Chemical andbiological evaluation of extracts and compounds from Echinacea pur-purea]. Dansk Kemi 2001;82:10-13.
Stærk D, Lemmich E, Franzyk H, Lemmich J, Christensen SB,Jaroszewski JW. Moderne naturstofkemi: Effektiv analyse af naturensstofbiblioteker [Modern natural products chemistry: Efficient analysis ofnatural compound libraries]. Lægemiddelforskning 2000;6-7.
Vogensen SB, Stensbøl TB, Egebjerg J, Frydenvang K, JohansenTN, Krogsgaard-Larsen P. Design af lægemidler mod Alzheimerssygdom [Design of drugs for the treatment of Alzheimers disease].Lægemiddelforskning 2000;30-31.
Wenckens M, Vedsø P, Begtrup M, Jakobsen P. Håb om bedre be-handling af brystkræft [Search for improved pharmaceuticals for treat-ment of mammary cancer]. Lægemiddelforskning 2001;14-15.
DEPARTMENT OF PHARMACEUTICS
Bagger MA, Nielsen HW, Bechgaard E. Nasal bioavailability of pep-tide T in rabbits: absorption enhancement by sodium glycocholate andglycofurol. Eur J Pharm Sci 2001;14:69-74.
Bjerregaard S, Wulf–Andersen, Stephens RW, Lund RL,Vermehren C, Söderberg I, Frokjaer S. Sustained elevated plasmaaprotinin concentration in mice following intraperitoneal injections ofw/o emulsions incorporating aprotinin, J Contr Release 2001;71:87-98.
Bjerregaard S, Söderberg I, Vermehren C, Frokjaer S. Acceleratedstability testing of a water-in-oil emulsion, J Disper Sci Tech 2001;22:23-31.
Bjerregaard S, Pedersen H, Vedstesen H, Vermehren C,Söderberg I, Frokjaer S. Parenteral water/oil emulsions containinghydrophilic compounds with enhanced in vivo retention: formulation,rheological characterisation and study of the in vivo fate using wholebody gamma-scintigraphy, Int. J Pharm 2001;215:13-27.
Bjerregaard S, Vermehren C, Soderberg I, Frokjaer S. Acceleratedstability testing of a water-in-oil emulsion. J Disper Sci Tech2001;22:23-31.
Bønløkke L, Hovgaard L, Kristensen HG, Knutson L, Lennernäs H.Direct estimation of the in vivo dissolution of spironolacton, in two par-ticle sizes, using single pass perfusion technique (loc-I.Gut). Eur JPharm Sci 2001;12:239-250.
Christensen KL, Pedersen GP, Kristensen HG. Preparation of redis-persible dry emulsions by spray drying. Int J Pharm 2001;212:187-194.
Christensen KL, Pedersen GP, Kristensen HG. Technical optimiza-tion of redispersible dry emulsions. Int J Pharm 2001;212:195-202.
Davidsen J, Vermehren C, Frokjaer S, Mouritsen OG, Jørgensen,K. Drug delivery by phospholipase A2 degradable liposomes. Int JPharm 2001;214:67-69.
Davidsen J, Vermehren C, Frøkjær S, Mouritsen OG, Jørgensen K.Enzymatic degradation of polymer Covered SOPC-liposomes in rela-tion to drug delivery. Advances in Colloid and Interface Science 89-90.2001: 303-311.
Friedrichsen G, Nielsen CU, Steffansen B, *Begtrup M. Model pro-drugs for the intestinal peptide transporter. A synthetic approach forcoupling of hydroxy-containing compounds to dipeptides. Eu J PharmSci 2001;14:13-19.
Hahn TW, Henneberg SW, Holm-Knudsen RJ, Eriksen K,Rasmussen SN, Rasmussen M. Pharmacokinetics of rectal paraceta-mol after repeated dosing in children. BJA 2000;85(4):512-9.
Hansen M, Christrup LL, Jarløv JO, Kampmann JP, Bonde J.Gentamicin dosing in critically ill patients Acta Anaesthesiol Scand2001;45(6):734-740.
Holm R, Müllertz A, Høy GE, Kristensen HG. Comparison of the to-tal bioavailability and the lymphatic absorption of halofantrine fromthree different unsaturated triglycerides in lymph-canullated conciousrats. Eur J Pharmci 2001;14:331-338.
Holm P, Schæfer T, Larsen C. End-point detection in a wet granula-tion process. Pharm Dev Technol 2001;6:151-162.
Holm R, Müllertz A, Pedersen GP, Kristensen HG. Comparison ofthe lymphatic transport of halofantrine administered in disperse sys-tems containing three different unsaturated fatty acids. Pharm Res2001;18:1299-1304.
Johansen A, Schæfer T. Effects of interactions between powder par-ticle size and binder viscosity on agglomerate growth mechanisms in ahigh shear mixer. Eur J Pharm Sci 2001;12:297-309.
Johansen A, Schæfer T. Effects of physical properties of powder par-ticles on binder liquid requirement and agglomerate growth mecha-nisms in a high shear mixer. Eur J Pharm Sci 2001;14:135-147.
Kristensen J, Schæfer T, Kleinebudde P. Direct pelletization in a ro-tary processor controlled by torque measurements. II: Effects ofchanges in the content of microcrystalline cellulose. AAPS Pharmsci. 2(3) (2000) article 24.
Lindhardt K, Ravn C, Gizurarson S, Bechgaard E. Intranasal ab-sorption of buprenorphine - in vivo bioavailability study in sheep. Int JPharm 2000;205:159-63.
Lindhardt K, Bagger M, Andreasen KH, Bechgaard, E. Intranasalbioavailability of buprenorphine in rabbit correlated to sheep and man.Int J Pharm 2001;217:121-26.
Lindhardt K, Gizurarson S, Stefánson SB, Òlafsson DR,Bechgaard EB. Electroencephalographic effects and serum concen-trations after intranasal and intravenous administration of diazepam tohealthy volunteers. Br J Clin Pharmacol 2001;52:521-27.
Luukkonen P, Schæfer T, Podczeck F, Newton M, Hellén L,Yliruusi J. Characterization of microcrystalline cellulose and silicifiedmicrocrystalline cellulose wet masses using a powder rheometer. Eur JPharm Sci 2001;13:143-149.
Møller-Sonnergaard J. Investigation of a new mathematical model forcompression of pharmaceutical powders. Eur. J Pharm Sci2001;14:149-157.
PUBLICATIONS
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Nielsen CU, Andersen R, Brodin B, Frokjaer S, Steffansen B.Model prodrugs for the intestinal oligopeptide transporter: model re-lease in aqueous solution and in various biological media. J ControlRel 2001;73:21-30.
Nielsen CU, Amstrup JSteffansen, B Frokjaer, S and Brodin, B.Epidermal growth factor inhibits glycylsarcosine transport and hPepT1expression in a human intestinal cell line, Am J Physiol GastrointestLiver Physiol 2001;281:G191-G199.
Nielsen L, Frokjaer S, Carpenter JF, Brange J. Studies of the struc-ture of insulin fibrils by Fourier transform infrared (FTIR) spectroscopyand electron microscopy, J Pharm Sci 2001;90:29-37.
Nielsen CU, Andersen R, Brodin B, Frokjaer S, Taub ME,Steffansen B. Dipeptide model prodrugs for the intestinal oligoepptidetransporter. Affinity for, and transport via hPepT1 in the human intesti-nal Caco-2 cell line. J Control Rel 2001;76:129-138.
Nielsen CU, Andersen R, Brodin B, Frokjaer S, Steffansen B.Model prodrugs for the intestinal oligopeptide transporter: model drugrelease in aqueous solution and in various biological media. J ControlRel 2001;73:21-30.
Nielsen CU, Amstrup J, Steffansen B, Frokjaer S, Brodin B.Epidermal growth factor (EGF) inhibits glycylsarcosine (Gly-Sar) trans-port and hPepT1 expression in human intestinal cell line. Am J PhysiolGastrointest Liver Physiol 2001;281:G191-G199.
Nielsen PB, Müllertz A, Norling T, Kristensen HG. The effect of �-tocopherol on the in vitro solubilisation of lipophilic drugs. Int J Pharm 2001;222:217-224.
Nielsen PB, Müllertz A, Norling T, Kristensen H.G. Comparison ofthe lymphatic transport of a lipophilic drug from vehicles containing �-tocopherol and/or triglyceride in rats. J Pharm Pharmacol2001;53:1439-144.
Nielsen L, Khurana R, Coats A, Frokjaer S, Brange J, Vyas S,Uversky VN, Fink AL. The effect of enviromental factors on the kinet-ics of insulin fibril formation: Elucidation of the molecular mechanism.Biochemistry 2001;40:6036-6046.
Nielsen L, Frokjaer S, Brange J, Uversky VN, Fink AL. Probing theMechanism of Insulin Fibril Formation with Insulin Mutants.Biochemistry 2001;40:6036-6046.
Nielsen HW, Bechgaard E, Twile B, Didriksen E, Almtorp GT.Solubilisation and stability of bumetanide in vehicles for intranasal ad-ministration, a pilot study. Pharm Devel Technol 2001;6(2):145-49.
Overgaard ABA, Højsted J, Hansen R, Møller-Sonnergaard J,Christrup LL. Patients evalution of shape, size and colour of soliddosage forms. Pharm World Sci 2001;23(5):185-188.
Overgaard ABA, Moeller-Sonnergaard J, Christrup LL, Hoejsted J,Hansen R. Patients’ evaluation of shape, size and colour of soliddosage forms. Pharm World Sci 2001;23:185-188.
Pedersen TB, Sabra MC, Frokjaer S, Mouritsen OG, Jørgensen K.Association of Acylated cationic Deca-peptides with DPPS-DPPCLipid Membranes, Chem Phys Lipids 2001;113:83-95.
Pedersen TB, Frokjaer S, Mouritsen OM, Jørgensen K. A calori-metric Study of Phoshocholine membranes mixed with desmopressinand its diacylated prodrug derivative (DDP), Int J Pharm (in press).
Pedersen TB, Sabra MC, Frokjaer S, Mouritsen OG, Jørgensen K.Association of an acylated model peptide with DPPC-DPPS lipidmembranes, Int J Pharm 2001;214:77-81.
Petersen FJ, Wørts O, Schæfer T, Sojka PE. Effervescent atomiza-tion of aqueous polymer solutions and dispersions. Pharm DevTechnol 2001;6:133-142.
Rømsing J, Østergaard D, Senderovitz T, Drozdziewicz D, SonneJ, Ravn G. Pharmacokinetics of oral diclofenac and acetaminophen inchildren after surgery. Paed Anaesth 2001;11:205-213.
Rømsing J, Mysager S, Vilmann P, Sonne J, Larsen NE,Østergaard D. Postoperative analgesia is not different after local vssystemic administration of meloxicam in patients undergoing inguinalhernia repair. Can J Anesth 2001;48:978-98.
Schæfer T. Growth mechanisms in melt agglomeration in high shearmixers. Powder Technol 2001;117:68-82.
Seo A, Schæfer T. Melt agglomeration with polyethylene glycol beadsat a low impeller speed in a high shear mixer. Eur J Pharm Biopharm2001;52:315-325.
Vermehren C, Jørgensen K, Schiffelers R, Frokjaer S. Activity ofmammalian secreted phospholipase A2 from inflammatory peritonealfluid towards PEG-liposomes. Early indications. Int J Pharmaceut2001;214:93-98.
Zangenberg NH, Müllertz A, Kristensen HG, Hovgaard L. A dynam-ic in vitro lipolysis model. Part I. Controlling the rate of lipolysis by con-tinous addition of calcium. Eur J Pharm Sci 2001;14:115-122.
Zangenberg NH, Müllertz A, Kristensen HG, Hovgaard L. A dynam-ic in vitro lipolysis model. Part II. Dissolution of probucol and danazol. Eur J Pharm Sci 2001;14:237-244.
PHD THESES
Andersen G. Relations between morphine metabolism, pain and sideeffects during long term treatment.
Bjerregaard S. Parenteral water-in-oil emulsions as sustaquined re-lease systems for hydrophilic compounds.
Hahn TW. Acetaminophen (Paracetamol). Pharmacokinetics andAnalgetic Effect in Postoperative Patients.
Lindhardt K. Nasal drug delivery. Applicability of nasal administrationfor systemic delivery, preferentially concerning acute treatment.
Kristensen J. Direct pelletization in rotary Processors.
Nielsen CU. Intestinal Peptide Transporter mediated Drug delivery us-ing Stabilized Dipeptide Pro-moieties: Affinity, Transport, Drug Releaseand Regulation.
Nielsen BP. Tocopherol as an oral drug delivery system.
Qvist MH. Chemical Permeations Enhancers in Transdermal DrugDelivery Systems.
Wiberg-Larsson BI. Comminution of particulate solids in a MicrosRing Mill.
Zangenberg NH. Development of a dynamic lipolysis model
OTHER PUBLICATIONS
Andersen R. Stabillitet og transport af modelprodrug designet til denintestinale oligopeptidtransportør. [Stabillity and transport of a modelprodrug designed for the intestinal oligopeptide transporter] DanmarksFarmaceutiske Højskole 2000.
Bagger MA, Beckgaard E. Genvej til hjernen via næsen. [Short cut tothe brain via the nose] Lægemiddelforskning 2001;24-25.
Brodin B, Nielsen CU, Steffansen B, Froklaer S. Ind gennem tarm-cellerne via naturlige optagemekanismer [Drug absorption via carrierprotein in the small intenstine] Lægemiddelforskning 2000;20-21.
ANNUAL REPORT 2000–2001
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Foged C, Brodin B, Frokjaer S. Optagelse af nye vacciner i kroppensimmunceller. [Uptake of new types of vaccines in denoritic cells]Lægemiddelforskning 2000;32-33.
Hahn TW, Rasmussen SN, Rasmussen M. Korrekt dosering ved be-handling af børns smerter. [The right dosing in pain management inchildren] Lægemiddelforskning 2000;8-9.
Heydenreich-Winther A, Bryder K, Fomsgaard A, Hovgaard L.DNA-vacciner: Stort potentiale – store udfordringer. [DNA-vaccines:Potentials and challenges] Lægemiddelforskning 2000;4-5.
Holm R, Müllerts A, Kristensen HG. Ind gennem tarmens lymfesys-tem. [Lymphatic transport of drugs] Lægemiddelforskning 2001;26-27.
Høst J, Jørgensen FS, Christensen IT, Hovgaard L, Frøkjaer S.Computeren er medicinalindustriens krystalkugle. [The computer is thecrystal ball for medicinal industry] Lægemiddelforskning 2001;28-29.
Jacobsen J, Rassing MR. Ind via mundslimhinden med svag strøm.[Cromucosal drug delivery applying iontophoresis]Lægemiddelforskning 2000;18-19.
Pedersen TB, Frokjaer S, Mouritsen OG, Jørgensen K.Membranforankring og peptiders terapeutiske effekt. [Membrane asso-ciation in relation to the terapeutic effect and peptides]Lægemiddelforskning 2000;22-23.
Petersen, F.J., Kristensen, H.G., Wørts, O., and Schæfer, T. Nylovende teknik til forstøvning af lægemidler. [A new technique for at-omization of luquids] Lægemiddelforskning 2000;14-15.
Nielsen LH. Udvikling af en fysisk kemisk model af blod-hjerne barri-eren. [A physico-chemical blood brain barrierer model developmentstudies] Danmarks Farmaceutiske Højskole /NeuroSearch, September2000.
Sønderkær S, Hansen LL, Flink J, Frokjaer S. Proteiner somlægemidler. [Proteins as drugs] Lægemiddelforskning 2001;16-17.
PATENT APPLICATIONS
Jorgensen K, Davidsen J, Vermehren C, Frokjaer S. MouritsenOG. Lipid-based drug delivery systems containing phospholipase A2degradable lipid derivatives and the therapeutic uses thereof. WO01/58910.
Jorgensen K, Davidsen J, Vermehren C, Frokjaer S, MouritsenOG. Lipid-based drug delivery systems containing phospholipase A2degradable lipid derivatives for topical application to the skin WO01/76555.
Jorgensen K, Davidsen J, Vermehren C, Frokjaer S, MouritsenOG. Lipid-based drug delivery systems for targeting diagnosticsagents. WO 01/76644.
Jorgensen K, Davidsen J, Vermehren C, Frokjaer S, MouritsenOG. Lipid-based drug delivery systems containing phospholipase A2degradable lipid derivatives for medical use against parasitic infections.WO 01/76556.
DEPARTMENT OF PHARMACOLOGY
Alsbo CW, Kristiansen U, Møller FM, Hansen SL, Johansen FF.GABAA receptor subunit interactions important for benzodiazepine andzinc modulation: a patch-clamp and single cell RT-PCR study. Eur JNeurosci 2001;13:1673-1682.
Ashina M, Bendtsen L, Jensen R, Jansen-Olesen I, Schifter S,Olesen J. Plasma levels of calcitonin gene-related peptide in chronictension-type headache. Neurology 2000;55:1335-1340.
Banke TG, Greenwood J, Christensen JK, Liljefors T, SchousboeA, Pickering DS. Identification of amino acid residues in GluR1 re-sponsible for ligands binding and desensitization. J Neurosci2001;21:3052-3062.
Campiani G, Morelli E, Nacci V, Fattorusso C, Ramunno A,Novellino E, Greenwood J, Liljefors T, Griffiths R, Sinclair C,Reavy H, Kristensen AS, Pickering DS, Schousboe A, Cagnotto A,Fumagalli E, Mennini T. Characterization of the 1H-cyclopentapyrimi-dine-2,4(1H,3H)-dione derivative (S)-CPW399, as a novel, potent andsubtype-selective AMPA receptor full agonist with partial desensitiza-tion properties. J Med Chem 2001 in press.
Edvinsson L, Sams A, Jansen-Olesen I, Tajti J, Kane SA, RutledgeRZ, Koblan KS, Longmore J. Characterization of the effects of anon-peptide CGRP receptor antagonist in SK-N-MC cells and isolatedhuman cerebral arteries. Eur J Pharmacol 2001;415:39-44.
Elster L, Kristiansen U, Pickering D, Olsen RW, Schousboe A.Molecular determinants of desensitization and assembly of thechimeric GABAA receptor subunits (�1/�2) and (�2/�1) in combinationwith �2 and �2. Neurochem Int 2001;38:581-592.
Eltorp CT, Jansen-Olesen I, Hansen AJ. Release of CGRP fromguinea pig dura mater in vitro is inhibited by sumatriptan but unaffect-ed by nitric oxide. Cephalalgia 2000;20:838-844.
Engberg J, Jensen BL, Yenidunya AF, Brandt K, Riise E. Phage-display libraries of murine antibody Fab fragments. Lab manual on an-tibody engineering (ed. S. Dübel). Springer Verlag 2001;ISBN 3-540-41354:65-92.
Engberg J, Yenidunya AF, Clausen R, Jensen BL, Sørensen P,Kops P, Riise E. Human recombinant Fab antibodies with T cell re-ceptor-like specificities generated from phage display libraries.Methods in Molecular Medicine (eds. Krauss, J and Welschof, M.)Humana Press (in Press) 2001.
Frølund B, Tagmose L, Liljefors T, Stensbøl TB, Engblom C,Kristiansen U, Krogsgaard-Larsen P. A novel class of potent 3-isox-azolol GABAA antagonists: Design, synthesis and pharmacology. JMed Chem 2000;43:4930-4933.
Gegelashvili G, Robinson MB, Trotti D, Rauen T. Regulation of glu-tamate transporters in health and disease. Progress in Brain2001;132:267-286.
Gegelashvili G. Glutamate transporters: Adding new tunes to theneuron-glia orchestra. Neurochemistry news 2001;1:65-68.
Hansen SL, Ebert B, Kristiansen U. Effects of GABAA receptor par-tial agonists in primary cultures of cerebellar granule neurones andcerebral cortical neurones reflect different subunit compositions. Br JPharmacol 2001;133:539-549.
Hansen SH, Moesgaard B, Hansen HH, Petersen G. When andwhere are N-acyl-ethanolamine phospholipids and anandamideformed? Wld Rev Nutr Diet 2000;88:223-227.
Hansen HH, Ikonomidou C, Bittigau P, Hansen SH, Hansen HS.Accumulation of the anandamide precursor and other N-acyletha-nolamine phospholipids in infant rat models of in vivo necrotic andapoptotic neuronal death. J Neurochem 2001;76:39-46.
Hansen HH, Schmid PC, Bittigau P, Lastres-Becker I, BerrenderoF, Manzanares J, Ikonomidou C, Schmid HHO, Ramos JA,Fernándes-Ruiz JJ, Hansen HS. Anandamide, but not 2-arachi-donoylglycerol, accumulates during in vivo neurodegeneration. JNeurochem 2001;78:1415-1427.
Hansen SL, Ebert B, Fjalland B, Kristiansen U. Effects of GABA(A)receptor partial agonists in primary cultures of cerebellar granule neu-rones and cerebral cortical neurones reflect different receptor subunitcompositions. Br J Pharmacol 2001;133(4):539-549.
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Jansen-Olesen I, Kaarill L, Edvinsson L. Characterization of CGRP-1 receptors in the guinea pig basilar artery. Eur J Pharmacol2001;414:249-258.
Jensen JB, Lund TM, Timmermann DB, Schousboe A, PickeringDS. Role of GluR2 expression in AMPA induced toxicity in culturedmurine cerebral cortical neurones. J Neurosci Res 2001;65:267-277.
Johansen T, Hansen HS, Richelsen B, Malmlöf K. The obeseGöttingen minipig as a model of the metabolic syndrome: Dietary ef-fects on obesity, insulin sensitivity and growth hormone profile. JComp Med 2001;51:150-155.
Kruuse C, Rybalkin S, Khurana TS, Jansen-Olesen I, Olesen J,Edvinsson L. The role of cGMP related phosphodiesterases, PDE1and PDE5, in cerebral artery dilatation. Eur J Pharmacol 2001;420:55-65.
Larsen AH, Frandsen Aa, Treiman M. Upregulation of the SERCA-type Ca2+ pump activity in response to endoplasmic reticulum stress inPC12 cells. BMC Biochemistry 2001;2-4.
Lauritzen L, Hansen HS, Jørgensen MH, Michaelsen KF. The es-sentiality of long chains n-3 fatty acids in relation to postnatal develop-ment and function of the brain and retina. Prog Lipid Res 2000;40:1-94.
Paschen W, Frandsen Aa. Endoplasmic Dysfunction - a common de-nominator for cell injury in acute and degenerative diseases of thebrain?, Invited review J Neurochem 2001;79:719-725.
Reuter U, Bolay H, Jansen Olesen I, Chiarugi A, Sanches del RioM, Letourneau R, Theoharides TC, Weaber C, Moskowitz MA.Delayed inflammation in rat meanings: Implication for migraine patho-physiology. Brain 2001;124:2490-2502.
Sams Nielsen A, Ørskov C, Jansen Olesen I. Evidence for CGRPuptake in perivascular capsaicin sensitive nerve fibres. Br J Pharmacol2001;132:1145-1153.
Sams A, Knyiha´r-Csillik E, Engberg J, Szok D, Tajti J, Bodi I,Edvinsson L, Vecsei L, Jansen Olesen I. Calcitonin gene-relatedpeptide and adrenomedullin receptor populations in human lenticulstri-ate arteries: in vitro pharmacological and molecular investigations indifferent artery sizes. Eur J Pharmacol 2000;408:183-193.
Schousboe A. Pharmacological and functional characterization ofastrocytic GABA transport: A short review. Neurochem Res2000;25:1241-1244.
Schousboe A, Kanner B. GABA transporters: functional and pharma-cological properties. In: Glutamate and GABA Receptors andTransporters (J Egebjerg, A. Schousboe and P. Krogsgaard-Larsen,eds.). Taylor & Francis Publ. 2002;337-349.
Schousboe A, Waagepetersen HS. Glial cell biology. In: The New-born Brain - Scientific Basis and Clinical Applications (H. Lagercrantz,P. Evrard, M. Hanson and C. Roedeck, eds.). Cambridge UniversityPress. 2002 in press.
Schousboe A, Hansen GH, Carlson BX. Amino acid neurotransmit-ters as developmental signals. In: Brain and Behaviour in HumanDevelopment (Kalveboer, A.F. and Gramsbergen, A eds.). KluwerAcademic Publ The Netherlands. 2001;185-197.
Sheykhzade M, Nyborg NCB. Mechanism of CGRP-induced relax-ation in rat intramural coronary arteries. Br J Pharmacol2001;132:1235-1246.
Timmermann DB, Lund TM, Belhage B, Schousboe A. Localizationand pharmacological characterization of voltage dependent calciumchannels in cultured neocortical neurones. Int J Dev Neurosci2001;19:1-10.
Timmermann DB, Westenbrook RE, Schousboe A, Catterall WA.Distribution of high voltage-activated calcium channels in culturedGABAergic neurones from mouse cerebral cortex. J Neurosci Res2002;67 in press.
Waagepetersen HS, Qu H Schousboe A, Sonnewald U. Elucidationof the quantitative significance of pyruvate carboxylation in culteredcerebellar neurons and astrocytes. J Neurosci Res 2001 in press.
Waagepetersen HS, Shimamoto K, Schousboe A. Comparison ofeffects of DL-threo-�-benzyloxyaspartate (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (t-2,4-PDC) on uptake and release of[3H]-aspartate in astrocytes and glutamatergic neurons. NeurochemRes 2001;26:661-666.
Waagepetersen HS, Sonnewald U, Gegelashvili G, Larsson OM,Schousboe A. Metabolic distinction between vesicular and cytosolicGABA in cultured GABAergic neurones using 13C MRS. J NeurosciRes 2001;63:347-355.
Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A.Multiple compartments with different metabolic characteristics are in-volved in biosynthesis of intracellular and released glutamine and cit-rate in astrocytes. Glia 2001;35:246-252.
Zaganas I, Waagepetersen HS, Georgopoupolos P, Sonnewald U,Plaitakis A, Schousboe A. Differential expression of glutamate dehy-drogenase in cultured neurons and astrocytes from mouse cerebellumand cerebral cortex. J Neurosci Res 2001 in press.
PHD THESES
Hansen H.H. The impact of brain injury: Involvement of the system ofendocannabinoids ligands and receptors.
Sams-Nielsen A. Characterization of CGRP induced effects in humanand guinea pig cerebral arteries.
Sheykhzade M. Characterization of calcitonin gene-related peptide re-ceptor subtype and function in rat coronary arteries.
Timmermann D. Subcellular localization and pharmacological charac-terization of violtage-gated calcium channels in cultured neocorticalneurones.
OTHER PUBLICATIONS
Frølund SL, Kristiansen U, Stensbøl TB, Krogsgaard-Larsen P. Nynøgle til behandling af skizofreni? [A new strategy for treatment ofschizophrenia?] Lægemiddelforskning 2000;24-25.
Hansen HH, Hansen SH, Hansen HS. Hjernens cannabis-lignendestoffer modvirker celledød. [The endogenous cannabis-like com-pounds prevents cellular death]. Lægemiddelforskning 2000;26-27.
Hansen HS. Endocannabinoider og deres fosfolipidforstadier.Carlsbergfondet - Årsskrift [Endocannabinoids and their Phospholipidsprecursors]. Carlsbergfoundation - Yearbook 2001;42-47.
Lund TM, Christensen E, Schousboe A, Lund AM. Stofskifte syg-domme - fra gen til terapi. Lægemiddelforskning [Metabolic diseases -from gene to therapy]. Lægemiddelforskning 2001;12-13.
Moesby L, Tommerup L, Hansen EW, Christensen JD. Kontrol aflægemidler for feberfremkaldende stoffer. Lægemiddelforskning[Control of pharmaceutical products for fever inducing substances].Lægemiddelforskning 2000:12-13.
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DEPARTMENT OF SOCIAL PHARMACY
PEER REVIEW PUBLICATIONS
Almarsdóttir AB, Morgall JM, Grímsson A. Professional responsibili-ty for the patient’s welfare - is it possible to legislate pharmaceuticalcare? J Soc Adm Pharm 2001;18:45-50.
Bissell P, Stig Haugbølle L, Morgall Traulsen J. An introduction tosociology – and what it can do for pharmacy practice research. Int JPharm Pract 2001;9:289-95.
Björnsdóttir I, Hansen EH. Telephone prescribing of antibiotics:General practitioners’ views and reflection. Eur J Public Health2001;11:260-3.
Karkee SB. Quality of drug provision from a philosophy of scienceperspective. Bulletin of Nepal Pharmaceutical Association 2000;11:7-12.
Karkee SB, Gyldmark M. Study setting in a research on drug provi-sion at primary health care. GPAN Bulletin 2001;(5):31-40.
Karkee SB, Hansen EH. Approaches to quality in drug provision.GPAN Bulletin 2000;(4):29-34.
Karkee SB, Hansen EH. Literature review on provision of antibacteri-als in primary health care in Nepal. Bulletin of Nepal PharmaceuticalAssociation 2001;12:35-46.
Morgall Traulsen J, Björnsdóttir I. Confidentiality – an issue forwhom? Focus group interviews with the lay public in Iceland. In:Institut für Technikfolgenabschätzung und Systemanalyse, editors.Innovations for an e-society. Challenges for technology assessment.Federal Ministry of Education and Research 2001. Available from: http://www.itas.fzk.de/e-society/preprints/contents.pdf(appears in Session 4: “e-health”).
Møldrup C, Morgall JM. Risks of future drugs: A Danish expertDelphi. Technological Forecasting and Social Change 2001;67:273-89.
Møldrup C, Morgall JM. Risk society reconsidered in a drug context– the emergence of medically enhanced normality. Health, Risk &Society 2001;3:59-74.
Møldrup C, Morgall JM, Almarsdóttir A. Citizens involvement in drugresearch and development - Danish citizens Delphi. Foresight2000;5:452-62.
Nørgaard LS, Morgall JM. The social construction of a drug interac-tion screening program – expectations and change in Danish pharma-cy practice. J Soc Adm Pharm 2000;17:110-17.
Nørgaard LS, Sørensen EW, Morgall JM. Social constructivist analy-sis of a patient medication record experiment – why a good idea andgood intentions are not enough. Int J Pharm Pract 2000;8:237-46.
Skinhoj KT, Larsson S, Helweg-Joergensen S, Hansen EH.Experiences of long-term tranquillizer use: A psychodynamic perspec-tive. Substance Use & Misuse 2001;36(9&10):1165-86.
Trap B, Todd CH, Moore H, Laing R. The impact of supervision onstock management and adherence to treatment guidelines: a random-ized controlled trial. Health Policy and Planning 2001;16:273-80.
PHD THESES
Knudsen P. The experience of younger women with SSRI antidepres-sants - a user perspective. Copenhagen: The Royal Danish School ofPharmacy, Department of Social Pharmacy 2001.
Ndekha A. Strengthening community participation in schistosomiasiscontrol: lessons from the Guruve District (Zimbabwe) schistosomiasiscontrol programme using Phytolacca dodecandra (a plant mollusci-cide). Copenhagen: The Royal Danish School of Pharmacy,Department of Social Pharmacy 2001.
OTHER PUBLICATIONS
Andersen C, Hansen EH, Morgall J. Pharmaceutical care – Status inDanish community pharmacies. Farmaceuten 2000;12(19):19-20.
Brendstrup E, Launsø L, Langgaard H. Kræftpatienters alternativevalg. [Cancer patients’ alternative choice]. Mit Helbred 2001;6:4-9 andSocial Kritik 2001;76:44-51.
Grum C, Launsø L. Giv plads til forskning i alternativ behandling.[Make space for research on alternative treatment]. Feature article.Danmarks Amtsråd 2001;(Aug):18-19.
Hansen EH, editor. Lægemiddeldage 2000. [The Medical DaysConference 2000]. Er lægemidler sund økonomi? [Are drugs value formoney?]. Farmaceuten 2000;12(19):18-25.
Hansen EH, Holstein BE, Due P. Social class variation in medicineuse among adolescents. Farmakoepi-Nyt 2001;(13):7.
Hansen EH, Holstein BE, Due P, Currie C. Medicine use among 11-15-year-old girls and boys in 28 countries. Farmakoepi-Nyt2001;(13):8.
Hansen EH, Lunde P-K. Utvärdering av NEPIs verksamhet 1995 -2000. Utvärderingsrapport februari 2001. [Evaluation of NEPI’s activi-ties 1995-2000]. Evaluation Report February 2001. Stockholm: InNEPI Annual Report 2000. p. 3-7. Available from: http://www.nepi.net/
Knudsen P, Hansen EH, Morgall JM. Yngre kvinders brug af SSRI.[Young women’s use of SSRI]. Farmaceuten 2000;12(19):24-5.
Knudsen P, Hansen EH, Morgall JM. Fra ilden til asken med antide-pressiv medicin. [From the fire into the frying pan with antidepressantmedicine]. Lægemiddelforskning 2000:34-5.
Kruse PR, Møller N. De danske apotekers historie; vol 7. [The historyof the Danish pharmacies; vol 7]. København: DanmarksApotekerforening; 2001 (752 pp).
Kruse PR, Møller N. Apotekervæsenets historie i Danmark. [The his-tory of the pharmacy system in Denmark]. København: DanmarksApotekerforening; 2001 (152 pp).
Langgaard H, Launsø L, Haugaard C. Main themes in research onunconventional cancer treatment. A literature study. Townsend Letterfor Doctors and Patients 2001;(Aug/Sept):57-66.
Larsen JB. Kend spillets regler. [Know the rules of the game].Farmaceuten 2001;13(16):4-5.
Launsø L. FVUK – et frø af kræftforeningen Tidslerne. [FVUK - A seedof the cancer association The Thistle]. Tidslerne 2001;(1):19-22.
Launsø L. Døre der åbner sig: Om grænseoverskridende læger og far-maceuter i det danske sundhedsvæsen. [Doors opening: About physi-cians and pharmacists as boundary walkers in the Danish health caresystem]. Højbjerg: Forlaget Hovedland 2001 (196 pp).
Launsø L. Omstridt behandling uden mirakler. [Controversial treatmentwithout miracles] 2’eren. Scleroseforeningen 2001;(June 6):8-10 andTidsskrift for Norsk Forening for Multippel Sklerose 2001;2:6-8.
Launsø L, Langgaard H. Ukonventionel kræftbehandling I. Præmisserfor kræftbehandling og forskning. [Unconventional cancer treatment I.The premises for treatment and research]. Månedsskrift for PraktiskLægegerning 2001;79:957-60.
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Launsø L, Langgaard H. Ukonventionel kræftbehandling II.Kræftpatienters handlerum - et medicinsk og sociologisk forsknings-felt. [Unconventional cancer treatment II. Cancer patients’ scope of ac-tion – a medical-sociological field of research]. Månedsskrift forPraktisk Lægegerning 2001;79:1043-50.
Launsø L, Langgaard H. Den selvvisiterende patient. Om forståelse afbrug og virkninger af ukonventionel og konventionel kræftbehandling.[The self-referring patient. Understanding of cancer patients’ usageand experienced outcomes of unconventional treatment]. Social Kritik2000;68:69 -78.
Launsø L, Rieper O. Forskning om og med mennesker - forskn-ingstyper og forskningsmetoder i samfundsforskning. [Research aboutand with human beings – modes of research and research methods insocial science]. Copenhagen: Nyt Nordisk Forlag; 2000, 4th edition(236 pp).
Lindholm K, Toft T, Larsen LAA, Sørensen EW, Nørgaard LS.Development of advice to type 2 diabetics by community pharmacies.Abstract. Pharmacology & Toxicology 2001;89(Suppl 1):109.
Møldrup C. Skræddersyede lægemidler til individuelle genomer.[Tailor-made drugs for individual genomes]. Lægemiddelforskning2001:10-11.
Møldrup C. Fremtidens medicin er skræddersyet. [Future drugs aretailor-made]. Helse 2001;11:26-7.
Møldrup C. Vil doping være forbeholdt idrætsudøvere i fremtiden?[Will doping only be a part of sports in the future?]. Fremtidsorientering2001;3:8-11.
Møldrup C. Skal doping være forbeholdt idrætsudøvere? [Shoulddoping only be a part of sports?]. In: Hvorfor er det ikke tilladt atbruge doping? [Why is doping not allowed?]. Anti Doping Danmarksidekonference; 2001. p. 20-1. Available from: http://www.doping.dk
Møldrup C. Medicin til alle og mod alt. [Drugs to everybody and foreverything]. Helse 2000;(10):79,81.
Møldrup C. Fremtidens medicinske optimerede krop. [The medicaloptimized body of the future]. Feature article. Jyllands-Posten 2000Sept 14.
Nyland N, Donner JE, Christensen BC, Harvald B, Kruse PR,Permin H, editors. Dansk Medicinhistorisk Årbog 2000; vol 28.[Danish Medical History Yearbook 2000; vol 28]. København, Odense,Århus: Dansk Medicinsk-Historisk Selskab, Medicinsk HistoriskSelskab på Fyn, Jysk Medicinhistorisk Selskab; 2000 (238 p).
Nørgaard LS, Sørensen EW, Toft T, Larsen LA. Systematisk indsam-ling af data om patienters lægemiddelrelaterede viden, holdninger oghandlinger. (Systematic collection of data on patients’ drug relatedknowledge, attitudes and actions). Fynske Læger 2001 May:41-2.
Permin H, Christensen BC, Harvald B, Kruse PR, Nyland N,Petersen CB, editors. Dansk Medicinhistorisk Årbog 2001; vol 29.[Danish Medical History Yearbook 2001; vol 29]. København, Odense,Århus: Dansk Medicinsk-Historisk Selskab, Medicinsk HistoriskSelskab på Fyn, Jysk Medicinhistorisk Selskab; 2001 (261 p).
Rossing C, Hansen EH, Morgall JM. Farmaceutisk omsorg påapotekerne. [Pharmaceutical care in community pharmacies].Lægemiddelforskning 2001:38-9.
Sørensen EW. Development of pharmacy practice – with special fo-cus on implementation and learning processes. Abstract. Faculty ofPharmacy, Sofia, Bulgaria: Phuture. International PharmaceuticalStudents’ Federation 2000;(Suppl 1):12.
Timm H, Hansen HP, Morgall JM, Sigmund H. Patienten – felt-arbejde, interview- og spørgeskemaundersøgelser. [The patient - fieldwork, interview and questionnaire studies]. In: Kristensen FB, HørderM, Poulsen PB, editors. Metodehåndbog for Medicinsk
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Teknologivurdering. [Methodology manual for medical technology as-sessment]. Copenhagen: Centre for Evaluation and Health TechnologyAssessment; 2001. p. 36-55. (Two versions: Danish and English).
Toft T, Sørensen EW, Andersen U, Gundersen B, Herborg H,Jensen MJ et al. Development of advice to angina pectoris patientsby community pharmacies. Farmaceuten 2000;12(19):21-2.
Toft T, Lindholm K, Larsen LAA, Sørensen EW, Nørgaard LS.Development of advice to angina pectoris patients by communitypharmacies. Pharmacology & Toxicology 2001;89(Suppl 1):147.
Wilkenschildt M, Kruse PR. Kejserinden og hendes rejsende apotek.[The empress and her travelling pharmacy]. In: Wilkenschildt M.Kongelige klenodier og kuriositeter. [Royal treasures and curios].København: Lindhardt og Ringhof; 2001. p. 189-93, 232-42.
THE DANISH PHARMACEUTICAL LIBRARY
Munck J. Glade miljøkemikere og biofarmaceuter. [Contented environ-mental chemists and biopharmacists.] Plexus 2000;32(4):3-5.
Munck J. Klinisk farmaci. [Clinical pharmacy.] Plexus 2000;32(4):6-7.
Munck J. Information, IT og de nye studerende på DanmarksFarmaceutiske Højskole. [Information, IT and new students at RoyalDanish School of Pharmacy.] Plexus 2000;32(5):3-7.
Munck J. Ungt blod til naturstofkemigruppen. [New talent for naturalproduct chemistry group.] Plexus 2000;32(6):9-10
Munck J. Sven Erik Jørgensen – forskningsprofessor. [Sven ErikJørgensen – research professor.] Plexus 2000;32(6):11.
Munck J. Massivt ønske om aktiv personalepolitik fra Højskolens lek-torer. [Associate professors strongly urge active personnel policy forRoyal Danish School of Pharmacy.] Plexus 2001;33(1):3-6.
Munck J. Højskolens nye rektor. [New rector for Royal Danish Schoolof Pharmacy.] Plexus 2001;33(2):3-6.
Munck J. Aftale om ny løn for laboranterne. [New wage agreement forlaboratory technicians.] Plexus 2001;33(2):14-15.
Munck J. Et rektorat takker af. [A rector steps down.] Plexus2001;33(3):3-5.
Munck J. Tanker ved et sceneskifte. [Reflections on a change ofscene.] Plexus 2001;33(3):6-9.
Munck J. Ingen nye centerbevillinger til DFH. [No new centre fundingfor Royal Danish School of Pharmacy.] Plexus 2001;33(3):10.
Munck J. De Danske Apotekers Historie. [The History of DanishPharmacies.] Plexus 2001;33(3):11-13.
Munck J. Ny institutstruktur? [New departmental structure?] Plexus2001;33(4):3-4.
Munck J. Specialistuddannelsen i apotekspraksis. [Specialisation inpharmacy practice.] Plexus 2001;33(4):8-10.
Munck J. Studenternetværket. [The Student Network.] Plexus2001;33(4):12-13.
Munck J. Ny webmaster. [New webmaster.] Plexus 2001;33(4):30.
Munck J. Ole Bjerrum ny professor i farmakologi. [Ole Bjerrum newprofessor of pharmacology.] Plexus 2001;33(4):32-33.
Munck J. Hvad er der galt med eksamenssystemet? [What is wrongwith the exam system?] Plexus 2001;33(5):6-9.
Munck J. Skal nye farmaceutuddannelser løse behovet for flere farma-ceuter? [Should new pharmacy programmes solve the need for morepharmacists?] Plexus 2001;33(5):14-15.
Munck J. Danmarks Farmaceutiske Højskole er udnævnt til MarieCurie Training Site. [Royal Danish School of Pharmacy appointed aMarie Curie Training Site.] Plexus 2001;33(5):21.
Munck J. FKL. Levedygtigt center har passeret de første to år. [Viablecentre survives first two years.] Plexus 2001;33(5):32.
Munck J. Ministermøder med undervisningsminister MargretheVestager. [Meeting Margrethe Vestager, Minister of Education.] Plexus2001;33(5):33-36.
Munck J. De nye farmaceutstuderende. Ansættelse i det offentligevirker ikke tillokkende. [New pharmacy students: public sector jobs notfirst priority.] Plexus 2001;33(6):16-17.
Munck J. Højskolens nye hjemmeside. [New website for Royal DanishSchool of Pharmacy.] Plexus 2001;33(6):28-30.
Munck J, Fjalland I. Integration af fremmedsprogede studerende påde længerevarende videregående uddannelser. [Integration of non-na-tive Danish speakers into higher education programmes.] Plexus2001;33(6):22-23.
Munck J, Vester-Andersen L. DFHs informationsaktiviteter over forpotentielle studere. [Royal Danish School of Pharmacy’s informationinitiatives for potential students.] Plexus 2001;33(6):18-20.
Nørhede A. Er du tilfreds med biblioteket? [Are you satisfied with thelibrary?] Plexus 2000;32(6):21.
Nørhede A. Gratis adgang til patentdatabasen Derwent InnovationsIndex, DII. [Free access to patents. Derwent Innovations Index, DII isopen.] Plexus 2001;33(1):22.
Nørhede A. Elektroniske tidsskrifter bliver brugt.[Electronic journals areused.] Plexus 2001;33(1):12-13.
Nørhede A. Tilfreds med biblioteket? [Satisfied with the library?]Plexus 2001;33(2):20-21.
Nørhede A. Slut med trykte tidsskrifter? [Final curtain for hard-copyjournals?] Plexus 2001;33(3):15-16.
Nørhede A. Slut med katalogkort på Danmarks FarmaceutiskeBibliotek. [Card catalogue discontinued at the Danish PharmaceuticalLibrary.] Plexus 2001;33(4):36.
Nørhede A. Derfor mangler Danmarks Farmaceutiske Bibliotekpenge... [That’s why the Danish Pharmaceutical Library is short ofmoney…] Plexus 2001;33(4):24,26.
Nørhede A. Viden skal deles. Officiel åbning af Danmarks ElektroniskeForskningsbibliotek. [Knowledge must be shared. Official opening ofThe Danish Electronic Research Library.] Plexus 2001;33(5):4-5.
Nørhede A. Mere biblioteksservice til stud.pharm’erne. [More libraryservice for students at the Royal Danish School of Pharmacy.] Plexus2001;33(6):37.
Nørhede A. Brug biblioteket – find informationen! Kompendium.Biblioteksvejledning. Informationssøgning i trykte og elektroniske medi-er. Ny udg. Danmarks Farmaceutiske Bibliotek; 2001. [Use the library– find information!]http://www.dfh.dk/bibliotek/docs/BrugBiblioteket2001.pdf
Nørhede A, Steffensen R, Byrialsen L, Dahlstrøm-Nielsen P.Brugertilfredshed i de elektroniske biblioteker [User satisfaction in elec-tronic libraries].
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Master’s Theses
DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY
Allan C. Beck. Water-soluble prodrug derivatives of tertiary amines.Supervisors: Claus Selch Larsen and Karin Fredholt (H. Lundbeck A/S,Copenhagen).
Rikke Brønnum. Investigation of the influence of pesticides on thedentrification rate in wetlands. Supervisor: Sven Erik Jørgensen.
Anne Greve, Gitte Albæk Christensen. Udvikling af analysemetode tilbestemmelse af heroinmetabolitter i fuldblod (Development of anAnalytical Method for the Determination of Heroine Metabolites inWhole Blood). Supervisor: Erling Sonnich Thomsen.
Caroline Marie Hasted. Carbonate esters possessing fatty acid likestructures as model prodrug derivatives of phenol. Supervisors: JesperØstergaard and Claus Selch Larsen.
Mille Holst-Jørgensen. Risikovurdering af parabener i injek-tionsvæsker (Risk Assessment of Parabens in Injection Fluids).Supervisor: Erling Sonnich Thomsen.
Nakisa Jaleshgar. Determination of selenomethionine in tablets byGC-MS. Supervisor: Ole Jøns.
Lars Lundager Madsen. The use of ultrasonic nebulization in induc-tively coupled plasma mass spectrometry for the determination oforganohalogens. Supervisor: Bente Gammelgaard.
Lise Johanna Laurbjerg Nielsen. Effect of fatty acid chain length ofpoly(ethylene oxide)- block-poly(hexylaspartamide amino acid) micelleson the encapsulation and aggregation state of amphotericin B.Supervisors: Claus Selch Larsen and Glen S. Kwon (University ofWisconsin, Madison, USA).
Karen Marie Olesen, Jeanette Reschka. Analyse af benzylpenicillinog dets nedbrydningsprodukter ved anvendelse af HPLC og CE.Udvikling af metoder og nedbrydningsforsøg. Supervisor: JetteTjørnelund.
Rikke Engelbrecht Pedersen. Bionedbrydning af chlorphenoler medefterfølgende formulering af QSAR-modeller. Supervisors: FlemmingIngerslev and Sven Erik Jørgensen.
Henrik Quaade. Solubility of salts of p-substituted benzoic acids andN-methyl and N,N-dimethylbenzylamine- effect of para substituent onsolubility. Supervisors: Henrik Parshad and Claus Selch Larsen.
Peter Rasmussen, Morten Riis. Helicobacter pylori invasion of ep-ithelial cells mediated by proteins in fetal calf serum - protein bindingand invasion studies. Supervisors: Karen Krogsfelt, Statens SerumInstitut and Claus Selch Larsen.
Christian Skonberg. Evaluering af en Tamoxifen “Molecular ImprintedPolymer” til brug ved fastfase-ekstration, herunder udvikling af et
HPLC-system. Udvikling og validering af en HPLC-metode til kvantita-tiv bestemmelse af nogle substituerede benzoesyrer og deresglycinkonjugater til brug ved studier af kvantitative struktur-metabolisme forhold. Supervisor: Steen Honoré Hansen.
Sara Zarei. Ion-pair chromatography in selenium speciation.Supervisor: Ole Jøns.
DEPARTMENT OF MEDICINAL CHEMISTRY
Maria Bugge. Natriumafhængige højaffinitets glutamat transportører.[Sodiumdependent high-affinity glutamate transporters].Supervisor: Hans Bräuner-Osborne.
Pernille Chantal Canci. Parabener – et strukturstudie. [Parabenes – astructural study]. Supervisor: Karla Frydenvang.
Heidi Eller, Lea Maria Rønneberg. Isolering, identifikation og in vitroantimalaria screening af stoffer fra Soymida febrifuga. [Isolation, identi-fication and in vitro antimalarial screening of compounds from Soymidafebrifuga]. Supervisor: Ulla Wagner Smitt, Jerzy Jaroszewski.
Johan Faber, Petur Weihe Dalsgaard. Isolering og strukturopklaringaf malariaaktive naphthylisoquinolinalkaloider fra Ancistrocladus tan-zanienssis. [Antiplasmodial naphtylisoquinoline alkaloids fromAncitstrocladus tanzaniensis, isolation and structural elucidation].Supervisors: S. Brøgger Christensen, Per Mølgaard.
Christina Høy Fischer. Farmakologisk karakterisering af en rækkeligander for GABAA –receptorer. [Pharmacological characterization ofligands for GABAA-receptors]. Supervisor: Tine Bryan Stensbøl.
Christine Gunnergaard. Kinesiske lægeplanter som antioxidanter.[Chinese herbal drugs containing antioxidants]. Supervisor: SørenBrøgger Christensen.
Kasper Harpsøe, Marie-Louise West Haagensen. Evaluering afMultiSelect og MultiScore. En evaluering af nye procedurer for forud-sigelse af bindingskonformation og bindingsaffinitet. [Evaluation ofMultiSelect and MultiScore. An evaluation of new procedures forpredicting binding conformation and binding affinity]. Supervisor:Flemming Steen Jørgensen.
Birgitte Søndergård Hertz. Syntese af glycin analoger ud fra 1-hy-droxypyrazol. [Synthesis of glycin analogues from 1-hydroxypyrazole].Supervisor: Mikael Begtrup.
Susanne Ellen Høgh. Resolvering, konfigurationsbestemmelse ogenantiofarmakologi af (RS)-2-amino-2-(3-hydroxy-5-phenyl-4-isoxa-zolyl)eddikesyre [(RS)-phenyl-AMAA]. [Resolution, configurational as-signment and enantiopharmacology of (RS)-2-amino-2-(3-hydroxy-5-phenyl-4-isoxazolyl)acetic acid [(RS)-phenyl-AMAA]]. Supervisors: TineB. Stensbøl, Tommy N. Johansen.
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Søren Johnsen. Sæsonvariation af cichoriesyre og alkylamider iEchinacea purpurea. [Seasonal variation in the content of cichoric acidand alkamides from Echinacea purpurea]. Supervisor: Per Mølgaard.
Anette Lauritzen, Iben Skovgaard Lund. Æterisk olie i kantlyng,Cassiope tetragona. - Individuel og geografisk variation samt biologiskaktivitet af indholdsstoffer. [Essential oil in Cassiope tetragona. –Individual and geographical variation, biological activity of con-stituents]. Supervisors: Per Mølgaard, Anne Adsersen.
Jeannette Lauritzen, Lene Jørgensen. Etnofarmakologisk under-søgelse af 21 chilenske lægeplanter. [Ethnopharmacological screeningof 21 medicinal plants]. Supervisors: Per Mølgaard, Anne Adsersen.
Anne Kruse Lykkeberg. Cytotoksiske stoffer i lægemiddelplantenCynanchum vincetoxicum: isolering, strukturopklaring og farmakolo-gisk karakterisering af phenanthroindolizidin-alkaloider. [Cytotoxic com-pounds from the medicinal plant Cynanchum vincetoxicum: isolation,structural elucidation and pharmacological evaluation of phenanthroin-dolizidine alkaloids]. Supervisor: Dan Stærk.
Alma Mustafic, Dea Marie Melskens. Syntese af potentielle GABAAreceptor ligander. [Synthesis of GABAA receptor ligands]. Supervisor:Bente Frølund.
Mette Vorup Møller, Lars Filtenborg Kirk. Videreudvikling af in vitroassay til undersøgelse af stoffers antimalariske aktivitet. [Developmentof assay for assessment of antimalarial activity in vitro]. Supervisors:Jette Christensen, Jerzy W. Jaroszewski.
Tram Bich Thi Nguyen, Trang Ngoc Thi Tran. Undersøgelse af an-timikrobiel aktivitet i vietnamesiske lægeplanter. [Investigations of antimicrobial activities of medicinal plants from Vietnam]. Supervisors: UlfNyman, Ulla Wagner Smitt.
Anne Sophie Toftlund Nielsen, Lone Munch Ringgaard.Glutamatreceptorligander. Stereoselektiv syntese. [Glutamate receptorligands. Stereoselective synthesis]. Supervisors: Lotte Brehm, RasmusPrætorius Clausen.
Kim B. Poulsen. Design og syntese af 4-alkyl-homoibotensyreanaloger. [Design and synthesis of 4-alkyl-homoibotenic acid ana-logues]. Supervisor: Ulf Madsen.
Miquel Poulsen. Konstruktion og karakterisering af et randomiseretmutagent bibliotek af den calcium sensende receptor. [Constructionand characterization of a random saturation mutagenesis library in thecalcium sensing receptor]. Supervisor: Hans Bräuner-Osborne.
Malene Anderberg Radin. Hyben – et potentielt naturlægemiddelmod gigt. [Rose hip – a potential herbal medicine for the treatment ofrheumatism]. Supervisor: Lene Gudiksen.
Maria Alexandra Schrøder. Vin og hjerte-karsygdomme. [Wine andcardiovascular diseases]. Supervisor: Lene Gudiksen.
Keld Agerbæk Siiger. Fremstilling af (R/S) 2-amino-3-(1-hydroxypyra-zol-5-yl) propan syre. [Synthesis of (R/S) 2-amino-3-(1-hydroxypyrazol-5-yl) propane acid]. Supervisor: Mikael Begtrup.
Brian Skole. Isolering og strukturopklaring af potentielle malariaaktiveindholdsstoffer i Landolphia dulcis. [Isolation and structure elucidationof potential antimalarial constituents from Landolphia dulcis].Supervisors: Jerzy W. Jaroszewski, Dan Stærk.
Mehrnoush Tabatabai, Mahboubeh Dadkah Tehrani. Isolering ogstrukturopklaring af stoffer med in vitro antimalaria virkning fra Iranskeplanter. [Isolation and structure elucidation of compounds with in vitroantimalarial activity from Iranian plants]. Supervisor: Jerzy W.Jaroszewski.
Johanna Thulin, Line Thygesen. Antioxidativ effect of Echinacea pur-purea. [Antioxidative effect of Echinacea purpurea]. Supervisors: PerMølgaard, Leif Skibsted, Alan Mortensen.
Hanh Trung Ung, Han Ung. Antioxidativ aktivitet af hyben fraHunderose, Rosa canina L. og Rynket rose, R. rugosa Thunb. og iso-lering af stoffer med antioxidativ effekt. [Antioxidative activity of hipsfrom Rosa canina L. and R. rugosa Thunb. and isolation of antioxida-tive constituents]. Supervisors: Anne Adsersen, Ulla Wagner Smitt.
Petrine Wellendorph. Syntese og farmakologisk karakterisering afphilanthotoxiner og af potentielle calcium-receptor antagonister.[Synthesis and pharmacological characterization of philanthotoxins andpotential calcium-sensing receptor antagonists]. Supervisors: Jerzy W.Jaroszewski, Henrik Franzyk, Hans Bräuner-Osborne.
Erik Zobel. Nye ligander baseret på 1-hydroxypyrazol til stereoselektivsyntese. [New ligands for stereoselective synthesis based on 1-hydroxypyrazoleI]. Supervisor: Mikael Begtrup.
DEPARTMENT OF PHARMACEUTICS
Zahra Abassi, Nahid Abbasi: General principles of quality assuranceof pharmaceuticals and screening tests of tuberculosis and antimalariadrugs. Supervisors: Sabine Koppf-Kubel, WHO Geneva and H. G.Kristensen.
Anette Kildegaard Andersen, Lene Ejstrup Andersen: Monitoringblood flow in AV-fistulas. – Implementing and quality assurance of theUltrasound Dilution Method as a routine method for diagnosing steno-sis in AV-fistulas. Supervisors: Søren Ladefoged, H:S Rigshospitaletand Mette Rasmussen.
Rikke Andersen, Lisbeth Hjorth Nielsen: Evaluation of the transportacross the blood-brain barrier of cyclic prodrugs of an opiod peptideanalog using an in situ rat brain perfusion model. Supervisors: RonaldT. Borchardt, University of Kansas, USA and Bente Steffansen.
Charlotte Arp, Pernille Meldal: Transfer of medication lists – qualityassurance of procedures. Supervisors: Steffen Ulrik Friis, HelsingørHospital and Mette Rasmussen.
Peter Baade: Evaluation of the efficiency of different fluidisation coat-ing equipment at various humidities. Supervisors: Jørn Møller-Sonnergaard, Per Holm, H. Lundbeck A/S.
Tenna Bekker, Helle Houlberg Carlsen: Empirical Prophylaxis ofPost-operative Vomiting versus Structures Prophylaxis.Supervisors: Greg Roberts, Repatriation General Hospital, Adelaide,Australia and Mette Rasmussen.
Sune Bergstrøm: Granulation in different high-shear mixers.Supervisors: Dr. B. Rotthäuser, Aventis Pharma GmbH and H. G.Kristensen.
Mette Line Bergendorff: Preparation and characterisation of inulinencapsulated liposomes for buccal delivery: in vitro study of interactionbetween liposomes and methyl-�-cyclodextrin. Supervisors: CharlotteVermehren, Elias Fattal and Amèlie Bochot (Faculté de Pharmacie,Université Paris-Sud, France).
Charlotte Born: Stability of allergic extracts from Phleum pratenseand Dermatophagoides pteronyssinus in simulated salivary, simulatedgastric fluid and simulated intestinal fluid. Supervisors: Lise Lund ALKAbello and Bente Steffansen.
Bettina Bruun: Polymeric delivery of camptothecin analogs and rabbitcarboxylesterase. Supervisors: Camilla Foged and Birger Brodin.
Anders Christensen: Metabolism of Oxycodone in female SpragueDawley and Female Dark Agouti rat liver microsomes. Supervisors:Andrew Somogyi, University of Adelaide and Lona Christrup.
Saima Durrani: Adsorption of DNA onto cationic dendrimer labelledpolystyrene nanoparticles for gene delivery applications. Supervisors:Lise Lund and Birger Brodin.
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Kirstine Mindegaard Gommesen: Nutrial Support in Intensive CareUnit Patients. Supervisors: Birgitte Skov, Amtssygehuset i Herlev andLona Christrup.
Mette Grove: Formulation of D-vitamin analogues in Self EmulsifyingDrug Delivery systems and Self Microemulsifying Drug DeliverySystems. Supervisors: Sven Frøkjær, Gitte P. Pedersen, LeoPharmaceutical Products A/S.
Adam Guhle: Manufacturing and characterization of pharmaceuticalsalts of a few model drug compounds. Supervisors: L.-E Briggner,AstraZeneca R&D Lund and H. G. Kristensen.
Tue Hansen: Estimation of segregation in the manufacture of tabletsby direct compression. Supervisors: Per Holm, H. Lundbeck and H. G.Kristensen.
Mikael Hansen: Evaluation of the Effect of Implementation of thePharmacokintic Software MW/PHARM in the Dosing of Lithium.Supervisors: Helle Angelo Bispebjerg Hospital and Lona Christrup.
Mette Krogh Hansen, Stina Westergaard Hansen: DissolutionCharacteristics of Solid Dispersions with Hydroxypropyl Methylcellu-lose Phtalate. Supervisors: David Hayes, F. H. Faulding, Salisbury,Australia and Lona Christrup.
Susanne Hostrup: Liposomes as drug delivery system for acylatedpeptides. Supervisors: Sven Frøkjær, Simon Bjerregaard Jensen, NovoNordisk A/S.
Christina Jensen, Lærke Jacobsen: Comparison of crushingstrength testers. Supervisors: Jørn Møller-Sonnergaard, KennethLokind Novo Nordisk A/S.
Lone Friis Jensen, Mikala Holt-Pedersen: Investigation of peptidetransporter activity in buccal TR146 and intestinal Caco-2 cell culturemodels using glycylsarcosine and valacyclovir as substrates.Supervisors: Bente Steffansen, Carsten Uhd Nielsen and Hanne MørckNielsen.
Louise Moe Jönsson: The process of reformulating the Pentasa sup-pository 1 g. Supervisors: Birgitte Nisssen, Ferring Pharmaceuticals,Henning G. Kristensen.
Jeannet E.R. Kall: N-(2-hydoxypropyl)methacrylamide (HPMA) copoly-mers for targeted delivery of polyamine analogs. Supervisors: CamillaFoged and Birger Brodin.
Jakob Gjelstrup Kristensen: Strategic considerations on implementa-tion of quality-assurance relevant to development of new drugs to aglobal market. Supervisors: Jørn Møller-Sonnergaard, Eva De Bang,Morten Juul Sørensen Novo Nordisk A/S.
Lisbeth Kristensen: Optimisation of Permeability and SolubilityAssessment Systems: Potential Extrapolation of Early Screening Datato BSC Classification. Supervisors: Sven Frøkjær, Susanne Sønderkær,Mitchell Taub, Novo Nordisk A/S.
Jesper Lund Larsen: Stabilizing effects of metal ions on insulin hex-amers studied by differential scanning calorimetry. Supervisors: SvenFrøkjær, Peter Langballe, Novo Nordisk A/S.
BM Larsen, Woll JT. Buksis: A physicochemical in vitro model forblod brain barrier-modelling. 2001. Supervisor: Erik Bechgaard.
Jens Ahlefeldt-Laurvigen: Scaling up of a film coating process in aperforated drum, from laboratory scale to pilot scale. August 2000.Supervisors: Breian Knudsen, Novo Nordisk A/S and Torben Schæfer.
Anne-Mette Lilleøre, Lene Kjær: Preformulation aspect of micronisedsolids. Dry- and wet ball-milling of pharmaceutical solids followed byphysical characterisation focusing on the use of a combined micro-thermal analyser and atomic force microscope. Supervisors: SvenFrøkjær, Lars Erik Briggner and Marianne Svärd, AstraZeneca, Lund.
Lars Lundtorp: The use of subcellular liver fractions to predictmetabolic stability and Michaelis-Menten kinetics for a series of p38MAP kinase inhibitors. Supervisors: Sven Frøkjær, Kim Sonne LeoPharmaceutical Product A/S.
Line Torp Madsen, Lisbet Emmery Jørgensen: Metabolits ofMorphine and Hydromorphone in Patiens in Chronic Haemodialysisand in Chronic Pain Patients with Normal Renal Function. Supervisors:Ryan Hansen, Amtssygehuset i Herlev and Lona Christrup.
Line Madsen: Melt agglomeration in a high shear mixer with additionof molten binder by a nozzle. June 2001. Supervisors: Anette Seo andTorben Schæfer.
Kjersti Meling: Formulation and cosmetic evaluation of Water-in-oilemulsions. Supervisor: Margrethe Rømer Rassing.
Bente Nicolaysen, Sofie Paarup Kirkeby Nielsen: Design of an invitro release model with controlled liquid supply to Conteed F®.Supervisors: Kristina Jensen, Coloplast A/S and Bente Steffansen.
Mette Tholstrup Nielsen, Vibeke Rydlund Nielsen: Registration ofSide-Effects of the Treatment with Opioids. Supervisors: Anders SchouOlesen, Aalborg Sygehus Syd and Lona Christrup.
Thomas Berg Nielsen: Control of the granulation process in laborato-ry and production scale high shear mixers by power consumptionmeasurements. June 2001. Supervisors: Per Holm, H. Lundbeck A/Sand Torben Schæfer.
Anne Flachs Nielsen, Merethe Off: Crystallisation of insulin aspart.Supervisors: Jette Jacobsen and Lise Smith.
Kristian Østergaard Nielsen, Hanne Larsen: Patient-controlled anal-gesia in children. Supervisors: Janne Rømsing and Kjeld Schmiegelow,The State University Hospital.
Kristine Juul Nilsson, Louise Vendelbo Jacobsen: Medicine takingbehaviours in Type 2 diabetics at Walton Diabetes Centre. Supervisors:Dave Thornton, University Hospital Aintree, Liverpool, UK and MetteRasmussen.
Tanna Friis Nönnecke, Susanne Kristensen: Evaluation of MiniMental State Examinations (MMSE’s) as a Screening Tool for CognitiveDysfunction in Patients with Chronic Non-Malignant Pain. Supervisors:Jette Højsted, H:S Rigshospitalet and Lona Christrup.
Michael Norsell: Fast pellet disintegrating with a high drug load. Supervisors: Dr G. Hauch, Aventis Pharma GmbH and H. G.Kristensen.
Charlotte R. Paulsen: A study of the lipids in the TR146 cell culturemodel. Supervisors: Margrethe Rømer Rassing and Charlotte Adrian.
Mikala Holt-Pedersen, Lone Friis Jensen: Investigation of peptidetransporter activity in buccal TR-146 and intestinal Caco-2 cell culturemodels. Supervisors: Hanne Mørck Nielsen, Carsten Uhd Nielsen andBente Steffansen.
MH Olsen, SL Pedersen: Olfactory absorption – Study of flourescinetransport from the nasal cavity to the brain. 2001. Supervisor: ErikBechgaard.
Morten Becker Pedersen, Martin Schultz: Ondansetron: What valuein the new millenium at The Children’s Hospital at Westmead.Supervisors: Gwen Higgins and Judith Longworth, The Children’sHospital at Westmead, Sydney, Australia and Mette Rasmussen.
Martin Søe Rasmussen: Matrix tablets based on low vicous HPMC. Supervisors: Lone Nørgaard, Alpharma Ltd. and H. G. Kristensen.
Baljit Singh: Formulation of cationic dendrimer labelled gold particlesfor adsorption and delivery of plasmid DNA. Supervisors: Lise Lundand Birger Brodin.
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Arne Hagsten Sørensen: Comparison of valaciclovir and Glu(acv)-Sarprodrugs with affinity for hPepT1; stability, affinity and transport.Supervisors: Anne Engelbrecht Thomsen and Bente Steffansen.
Mette Thorvaldsen: Aminoglycoside Therapy at Intensive Care Unitsat Danish Hospitals. Supervisors: Jan Bonde, Amtssygehuset i Herlevand Lona Christrup.
Mette Thun: Liposomal stability against phospholipases – a drug de-livery aspect. Supervisors: Charlotte Vermehren, Harald S. Hansen(Dept. of Pharmacology).
Huong Tran, Maja Nøddekær: Formulation and characterization of ananoemulsion. Supervisor: Hanne Mørck Nielsen.
Signe Walmar, Mette Wulff: Aquous ethyl cellulose coating of granu-late for manufacturing of Penatasa tablets with a specified dissolutionprofile. Supervisors: Jørn Møller-Sonnergaard and Birgitte Nissen,Ferring A/S.
Henrik Ravn Aage: Characterization of moisture content in granuleswith regard to prediction of compaction properties. Supervisors:P.Mohr Olsen and P. Berthelsen, Nycomed Pharma and H. G.Kristensen.
DEPARTMENT OF PHARMACOLOGY
Dorthe Birgitte Andersen: Udvikling af kognitive modeller hos mus irelation til skizofreni. [Development of cognitive models in mice in rela-tion to schizophrenia]. Supervisor: Orla Miller Larsson.
Maria Paabøl Andersen: Effekter af henholdsvis akut og kronisk ad-ministration af antipsykotika på modellen for prepulse inhibering hosrotter. [Effects of chronic versus acute treatment with antipsychoticson the prepulse inhibition model in rats]. Supervisor: Orla MillerLarsson.
Jesper Bendtsen: Ekspression af c-fos hos rotter udsat for varme ogkolde omgivelser samt c-fos´ co-lokalisering med neurotensinrecptorer.[Expression of c-fos in rats during warm and cold environments and c-fos co-localization with neurotensine receptors]. Supervisor: BjarneFjalland.
Signe Farsø Bomholt: Effect of NS1231 in a mouse model of focalcerebral ischaemia. Supervisor: Bjarne Fjalland.
Jeanett Borsdal: Hypothermiske effekter af neurotensin, NT69L ogJMV 449 samt den neuroprotektive effekt af hypothermi forårsaget afJMV 449 ved fokal iskæmi. [Hypothermic effects of neurotensin,NT69L and JMV 449 and the neuroprotective effect of JMV 449 in-duced hypothermia in focal ischaemia]. Supervisor: Bjarne Fjalland.
Than Che, Jamila Tahtah: Stress inducerer NOS - Kvantificering afNOS mængden i rotter efter akut og kronisk stressbehandling. [Stressinduces NOS - Quantification of NOS in cerebral arteries and dura af-ter acute and chronic stress]. Supervisor: Inger Jansen Olesen.
Monika Christensen, Lene Landsgrav: Karakterisering af CGRP re-ceptorer i septale koronar arterier fra rotter. [Characterization of CGRPreceptors in septale coronary arteries from rats]. Supervisor: Niels C.Berg Nyborg.
Jesper Drøgemüller: DNA vaccine mod salmonella typhimurium infek-tion fremstilling samt afprøvning i Lewis rotter. [DNA vaccine againstsalmonella typhimurium infection design and testing in Lewis rats].Supervisors: Peter Thygesen and Erik S. Riise.
Anne Fjeldsted Eriksen, Pernille Saxov: Undersøgelse af Matrem-og Parthenolids virkningsmekanisme i migrænebehandling. [Studies ofthe mechanisms of action of Matrem (feverfew) and Parthenolide in re-lation to prophylatic treatment of migraine]. Supervisors: Per Mølgaardand Inger Jansen Olesen.
Mette Fryland: Immunologisk status ved depression og under antide-pressiv behandling. [Immunological status in Major depression andduring antidepressant treatment]. Supervisor: Bjarke Ebert.
Catrine Haugsted Høyer, Gitte Louise Juhl: Varmeinaktivering af py-rogen aktivitet i Bacillus subtilis endosporer. [Heat inactivation of pyro-genic activity in endospores of Bacillus subtilis]. Supervisors: Erik WindHansen and Lise Moesby.
Fida Issa: Cellulær lokalisering af glukagon-lignende peptid-1 recep-torer. [Cellular localization of glucagon-like peptide-1 receptors].Supervisor: Peter Thygesen.
Mikkel Rostgaard Jensen, Allan Astrup Kah: Kvantificering af Fos-positive neuroner som udtryk for nociception hos grise efter intra-muskulær injektion af viscoleo, sesamolie og frie fedtsyrer.[Quantification of Fos-positive neurones as a marker of nociception inpigs after intramuscular injection of Viscoleo, sesam oil and fattyacids]. Supervisor: Bjarne Fjalland.
Lars Ketilsson: Salbumatol induceret IL-6 udskillelse i pituicytter.[Salbumatol induced IL-6 release from pituicyt]. Supervisor: LiseMoesby.
Anne Louise Kirkegaard, Ditte Maria Karpf: Effect of ketoprofen andits enantiomers on the renal disposition of methotrexate in the isolatedperfused rat kidney. Supervisor: Bjarne Fjalland.
Rikke Larsen, Nina Bornhøft Nielsen: CGRP´s involvering i morfintolerance - in vitro forsøg med isolerede organer og neuroner.[Involvement of CGRP in tolerance to morphine - in vitro experimentswith isolated organs and neurones]. Supervisor: Bjarne Fjalland.
Annette Skovgaard Lund, Henrik Kjer Petersen: Gentamicin - do-sisjustering og farmakokinetik hos intensivpatienter. [Gentamicin -Therapeutic drug monitoring and Pharmacokinetics in critically ill pa-tients]. Supervisors: Mette Rasmussen and Søren Rasmussen.
Rikke Marie Lund: Screening for adjuvant effekt af diphthalater imurin injektionsmodel. [Screening for adjuvant effect of diphthalates ina murine injection model]. Supervisor: Peter Thygesen.
Jesper Mosolff Mathiesen: G-protein kobling af den humane neu-rokinin-2 receptor. [G-protein coupling aspects of the human neu-rokinin-2 receptor]. Supervisor: Arne Schousboe.
Christina Nielsen: Aktivering af Mono Mac 6 celler med lipopolysac-charid og lipoteichoinsyre. [Activation of Mono Mac 6 cells withlipopolysaccharide and lipoteichoin acid]. Supervisor: Lise Moesby.
Charlotte Ullitz Olesen, Tina Olesen: Elektrofysiologisk studie afGABAA receptoren. [Electrophysiological investigation of the GABAAreceptor]. Supervisor: Uffe Kristiansen.
Annemette Due Pedersen: LPS-induceret nitrogenoxid produktion idyrkede cellekulturer fra murine neurohypofyser. [LPS-induced releaseof nitrogenoxide by cultured cells from the murine neurohypophysis].Supervisor: Erik Wind Hansen.
Mikkel Pind: Identifikation af protein-protein interaktioner mellemGABAA receptor �4-subunit intracellulært domæne og et eller flere in-tracellulære proteiner ved brug af gærcelle-2-hybridsystemet. [Findingprotein-protein interactions between the �4-subunit intracellular loop ofthe GABAA receptor and one or several intracellular proteins affectingthe �4-subunit, using the yeast two-hybrid system]. Supervisor: ArneSchousboe.
Lone Rahbek, Camilla Recke: Funktionen af serum amyloid P kom-ponent hos patienter med systemisk lupus erythematosus. [Functionof serum amyloid P component in-patients with systemic lupus erythe-matosus]. Supervisor: Peter Thygesen.
Alan Sarup: Differential regulation of the expression of the glutamatetransporters GLT-1 and GLAST by soluble factors in cultures of astro-cytes and organotypic hippocampal slice cultures. Supervisor: ArneSchousboe.
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Christoffer von Sehested Schousboe: Synergistisk effekt mellemopioide- og cannabinoide receptorer i muse vas deferens. [Synergismbetween opioid- and cannabinoide receptors in the mouse vas defer-ens]. Supervisor: Bjarne Fjalland.
Anja Hviid Simonsen: Biokemiske markører i præklinisk forskning.udvikling af et enzym linked immunosorbent assay til måling af type IVcollagen i urin. [Biochemical markers in preclinical research develop-ment of an enzyme linked immunsorbent assay measuring type IV col-lagen fragments in urine]. Supervisor: Erik Wind Hansen.
Caja Skettrup: Modellering af farmakokinetiske parametre for stoffetNN703 i programmerne WinNonLin og NONMEM. [Modelling of phar-macokinetic parameters of NN703 in WinNonLin and NONMEM].Supervisor: Peter Thygesen.
Kristin Skogstrand: Serum amyloid P komponent hos patienter medsystemisk lupus erythematosus. [Serum amyloid P component in-patients with systemic lupus erythematosus]. Supervisor: PeterThygesen.
Ine Blankenberg Skotteheim, Tine Nystrup Stolpe: Studier vedrør-ende ekspression og funktion af UCP3. [Studies on the expressionand function of UCP3]. Supervisor: Arne Schousboe.
Anders Søhoel: Effects of CNS active drugs in animal models forlearning and memory. Supervisor: Bjarne Fjalland.
Helle Møller Sørensen, Annika Weber Rasmussen: Vurdering afsammenhængen mellem erythropoientin-resistent og TT-virus hos hæ-modialysepatienter. [Evaluation of the coherence between erythropoi-entin-resitance and TT-virus in hemodialysis patients]. Supervisors:Mette Rasmussen and Søren Rasmussen.
Peter Sørensen: Fremstilling af rekombinante antistof-reagenser medrelevans for patogenesen af dissemineret sklerose. [Generation of re-combinant antibodies of relevence for the pathogenesis of multiplesclerosis]. Supervisor: Jan Engberg.
Ann Kristina Thomsen, Kamilla Rolsted: Protonaktiverende Na+-kanaler og AMPA-receptorers betydning for degeneration af corticaleneuroner. [The role of proton activated Na+-channels and AMPA recp-tors in degeneration of cortical neurones]. Supervisor: Orla MillerLarsson.
Jeppe Voss: Rotarod studies of benzodiazepine/GABAA receptor ago-nists. Supervisor: Bjarne Fjalland.
DEPARTMENT OF SOCIAL PHARMACY
Janne Hjorth Henriksen: Danskernes brug af naturlægemidler – ogrelationer til helbred, sundheds- og sygdomsadfærd, uddannelse ogindkomst. [Use of herbal medicine within the Danish population – andrelations to health, health and illness behaviour, education and in-come]. Supervisor: Ebba Holme Hansen.
Karen Hoebeke, Christian Huyghe (Belgian SOCRATES students):Qualitative and quantitative analysis of the asthma therapeutic out-comes monitoring (TOM) projects held in Belgium and Denmark. Danish supervisor: Ellen Westh Sørensen. Belgian supervisor: Prof. Dr.Apr. Sophie Sarre (Vrije Universiteit Brussel).
Mette Faber Jensen: Indlægssedler – præparatrelateret og bruger-orienteret lægemiddelinformation. En sammenlignende analyse af ind-lægssedler i udvalgte EU-lande. [Patient information leaflets. Productrelated and user orientated drug information. A comparative analysis ofpatient information leaflets from selected EU-countries]. Supervisor:Poul R. Kruse.
Asger Svend Johansen: Danskernes holdninger til e-medicin.[Attitudes towards e-medicine within the Danish population – a so-ciodemographic profile]. Supervisor: Ebba Holme Hansen.
Pernille Larsen: Forsyningen af tuberkuloselægemidler i Nepal. [Thesupply of tuberculosis drugs in Nepal]. Supervisor: Ebba HolmeHansen.
Mikkel Nørreslet: ”De nye forbrugere” – Findes på apoteket! [The newconsumers” – Exist at the pharmacy!]. Supervisor: Janine MorgallTraulsen.
Majken Nørskov Petersen: Udbredelsen af “rationel farmakoterapi”på danske apoteker med hensyn til håndkøbslægemidler. [Diffusion of“rational pharmacotherapy” on Danish community pharmacies in re-gard to non-prescription drugs]. Supervisor: Lotte Stig Haugbølle.
Bertel Rüdinger: Fra elfenbenstårn til økonomisk faktor – De danskeuniversiteter under globaliseringen. [From the ivory tower to an eco-nomic factor – Danish universities in the light of globalisation]. Super-visor: Janine Morgall Traulsen.
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MASTER’S THESES
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ANNUAL REPORT 2000–2001
Staff
THE ROYAL DANISH SCHOOL OF PHARMACY
Universitetsparken 2
DK-2100 Copenhagen
Phone: +45 35 30 60 00
Fax: +45 35 30 60 01
Internet: www.dfh.dk
E-mail: [email protected]
(E-mail: initials followed by @dfh.dk)
HEADS OF SCHOOL
Rector
Povl Krogsgaard-Larsen (rektor) Professor, DSc (pharm.) professor, dr.pharm.
Deputy Rector
Bjarne Fjalland (bf) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
MANAGEMENT
Administrator
Judith Christiansen (jc) MA cand.mag.
Head of Personnel Division
Elisabeth Riis (elri) MA (law) cand.jur.
Head of Study Division
Ilse Fjalland (if) MSc (pharm.) cand.pharm.
Head of the Study Board
Jette Jacobsen (jeja) Associate Professor, MSc (pharm.) lektor, cand.pharm.
Head of the Budgeting and Accounting Division
Villy Dahl Jensen (vdj) MA cand.scient.pol.
Head of the Information Office
Jesper Munck (jemu) MA cand.mag.
Head of Library Services
Alice Nørhede (aln) Librarian DB1 bibliotekar DB1
PAGE 126
DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY
Departmental Board 2001
Head of Department: Professor Steen Honoré Hansen
Deputy Head of Department: Associate Professor Bent Halling-Sørensen
Professor Claus Selch Larsen
Laboratory Porter Court Schwerdfeger
Associate Professor Claus Cornett
PhD student Anne K. Lykkeberg (observer)
Student Jesper R. Bojsen
Secretariat
Helle Sigetty Bøje +45 35 30 62 61
Inge Miller +45 35 30 62 75
Søren Kragh +45 35 30 64 62
Fax: +45 35 30 60 10
Scientific Staff
Email: Initials followed by @dfh.dk
Andersen, Henrik Rasmus (hra) PhD student, MSc ph.d.-studerende, cand.scient.
Bendahl, Lars (labe) PhD student, MSc ph.d.-studerende, cand.scient.
Brix, Rikke (ribr) PhD student, MSc ph.d.-studerende, cand.scient.
Brøndsted, Helle (hb) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Cornett, Claus (cc) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Eberth, Kirsten (ke) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Farver, Ole (of) Professor, DSc professor, dr.scient.
Gammelgaard, Bente (bg) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Hagen, Nina (nh) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Halling-Sørensen, Bent (bhs) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Hansen, Steen Honoré (shh) Professor, DSc (pharm.) professor, dr.pharm.
Ingerslev, Flemming (fi) Assistant Professor, Msc (pharm.) adjunkt, ph.d., cand.polyt.
Jacobsen, Anne-Marie (amja) Research Assistant forskningsassistent
Jensen, Berit Packert (bpj) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Johannessen, Jane K. (jkj) Assistant Professor, Msc (pharm.) adjunkt, cand.pharm.
Jøns, Ole (oj) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Jørgensen, Sven Erik (sej) Associate Professor, Dsc docent, dr.scient.
Kristensen, Mads Gjelstrup (mgk) Assistant Professor, Msc (eng.) amanuensis, cand.polyt.
Larsen, Claus Selch (csl) Professor, DSc (pharm.) professor, dr.pharm.
Larsen, Susan Weng (swe) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Loke, Marie-Louise (mlc) PhD student, MSc ph.d.-studerende, cand.scient.
Lykkeberg, Anne Kruse (ak) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Nielsen, Anders Bach (abn) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Nielsen, Søren Nors (snn) Associate Professor, PhD lektor, ph.d. (scient.)
Olesen, Karen-Marie (kmo) University Instructor amanuensis
Olesen, Mogens Nørgaard External Associate Professor, MSc ekstern lektor, cand.scient.
Olsen, Jørgen (jo) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Parshad, Henrik (hpa) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Sidenius, Ulrik (ulsi) Assistant Professor, MSc adjunkt, cand.scient.
Skonberg, Christian (cs) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Steinicke, Ann-Louise (alsl) Research Assistant forskningsassistent
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STAFF
Departmental Board 2002
Head of Department: Professor Steen Honoré Hansen
Deputy Head of Department: Associate Professor Bent Halling-Sørensen
Associate Professor Bente Gammelgaard
Senior Laboratory Technician Tove Eckhardt
PhD student Anne K. Lykkeberg (observer)
Student Rune Gildsig
Thomsen, Erling Sonnich (est) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Zhang, Jingjie (jz) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Østergaard, Jesper (joe) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Teaching Assistants
Gerd Askaa, Hans Bjerge, Jens Corfitzen, Frank Hansen, Poul Einer Hansen, Henning Brandt Jensen, Inger Spangsberg Jensen, Niels Rhod
Larsen, Mette Sandby Holkenfeldt, Kirsten Rald, Jeanette Reschka
Administative and technical staff
Andersen, Kirsten (ka) Senior Laboratory Technician laboratorieoverassistent
Bech, Lioubov (lib) Trainee, Laboratory Technician laborantpraktikant
Bøje, Helle Sigetty (hsb) Head of Section kontorfuldmægtig, cand.negot.
Eckhardt, Tove (te) Senior Laboratory Technician laboratoriefuldmægtig
Hansen, Karen Margrethe (kmh) Senior Laboratory Technician laboratoriefuldmægtig
Hansen, Torben Lindholm (tlh) Assistant Engineer, Tool Maker ingeniørassistent, værktøjsmager
Hermansen, Susanne (suhe) Senior Laboratory Technician laboratorieoverassistent
Jabin. Suraya (sj) Laboratory Technician laborant
Jochimsen, Lars Halldor (lhj) Electrical Engineer elektronikmekaniker
Kongsbach, Anette Due (adk) Senior Laboratory Technician laboratorieoverassistent
Konstantinovitsch, Carina (cacon) Trainee, Laboratory Technician laborantpraktikant
Kragh, Søren (skr) Clerk kontorassistent
Larsen, Bente (bela) Laboratory Technician laborant
Larsen, Ninna Kjær Cleaner rengøringsassistent
Laursen, Anni Bonde (abl) Cleaner rengøringsassistent
Lind, Nina Cleaner rengøringsassistent
Lunow, Elzbieta (ellu) Laboratory Technician laborant
Miller, Inge (im) Senior Clerk overassistent, ED
Milosevic, Melita Cleaner rengøringsassistent
Schwerdfeger, Court (csc) Laboratory Porter laboratoriemester
Vejlemand, Nina Støber (nsv) Laboratory Engineer laboratorietekniker
DEPARTMENT OF MEDICINAL CHEMISTRY
Departmental Board 2001
Head of Department: Associate Professor Ulf Madsen
Deputy Head of Department: Associate Professor Søren Brøgger Christensen
Associate Professor Flemming Steen Jørgensen
Associate Professor Per Mølgaard
Professor Mikael Begtrup
Cleaner Merete Axkær (observer)
Senior Laboratory Technician Bente Gauguin
Assistant Engineer, Precision Mechanic Karsten Klint
PhD student Hanne Ziegler (observer)
Student Behzad Ghorbani
Secretariat
Main floor:
Anne Lisbeth Frederiksen +45 35 30 62 51
Anne M. Lund +45 35 30 62 91
Fax: +45 35 30 60 41
PAGE 128
ANNUAL REPORT 2000–2001
Departmental Board 2002
Head of Department: Professor Jerzy Jaroszewski
Associate Professor Jette S. Kastrup
Deputy Head of Department: Associate Professor Ulf Madsen
Senior Laboratory Technician Bente Gauguin
Assistant Engineer, Precision Mechanic Karsten Klint
Student Thomas Høgh Jensen
First floor:
Anne-Mette Nielsen +45 35 30 62 41
Second floor:
Anne Nordly +45 35 30 65 11
Fax: +45 35 30 60 40
Scientific Staff
Email: Initials followed by @dfh.dk
Abrahamsen, Bjarke (ba) Scholar student scholarstipendiat, stud.pharm.
Adsersen, Anne (aad) Associate Professor, MSc (pharm.) lektor, cand.pharm.
Akinleminu, Tine T. (titiak) Research Assistant, MSc (pharm.) forskningsassistent, cand.pharm.
Begtrup, Mikael (mb) Professor, PhD (tech.) professor, ph.d. (tech.)
Bräuner-Osborne, Hans (hbo) Professor, PhD (pharm.) professor, ph.d. (pharm.)
Brehm, Lotte (lb) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Brown, Lea Dalby (ldb) PhD student, MSc ph.d.-studerende, cand.scient.
Bunch, Lennart (lebu) PhD student, MSc ph.d.-studerende, cand.scient.
Buur, Jette Byberg (jbb) School Manager, Associate Research Professor, PhD (pharm.) forsk.skoleleder, forsk.lektor, ph.d. (pharm.)
Cali, Patrizia (paca) PhD student, MSc ph.d.-studerende
Christensen, Søren Brøgger (sbc) Associate Professor, PhD (pharm.) docent, ph.d. (pharm.)
Clausen, Rasmus Prætorius (rpc) Assistant Research Professor, PhD forskningsadjunkt, ph.d (scient.)
Duker-Eshun, George (gedu) PhD student, MSc ph.d.-studerende
Elm, Peter Larsen (pem) Research Assistant, MSc forskningsassistent, cand.scient.
Eskildsen, Jørgen (jes) PhD student, MSc ph.d.-studerende, cand.scient.
Franzyk, Henrik (hf) Associate Professor, PhD lektor, ph.d. (scient.)
Frydenvang, Karla (kf) Associate Research Professor, PhD (pharm.) forskningslektor, ph.d. (pharm.)
Frølund, Bente (bfr) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Greenwood, Jeremy R. (jgr) Assistant Research Professor, PhD forskningsadjunkt, ph.d. (med.)
Gudiksen, Lene (lg) Associate Professor, MSc (pharm.) lektor, cand.pharm.
Guldbrandt, Mette (mgu) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Hansen, Tom Børsen (tbh) PhD student, MSc ph.d.-studerende, cand.scient.
Hermit, Mette B. (mebh) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Hertz, Else Birgitte S. University Instructor, MSc (pharm.) amanuensis, cand.pharm.
Hogner, Anders (ah) PhD student, MSc ph.d.-studerende
Jakobsen, Carsten M. (cja) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)
Jaroszewski, Jerzy W. (jj) Professor, PhD professor, ph.d. (scient.)
Jensen, Anders A. (aaj) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)
Jensen, Birthe (bj) Associate Professor, DSc (pharm.) lektor, dr.pharm.
Jensen, Heidi Dorte (hdj) PhD student, MSc (food chemistry) ph.d.-studerende, cand.tech.al.
Johansen, Tommy Nørskov (tnj) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Jørgensen, Anne Techau (atj) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Jørgensen, Charlotte Grube (chj) Research Assistant, MSc (eng.) forskningsassistent, cand.polyt.
Jørgensen, Flemming Steen (fsj) Associate Professor, PhD docent, ph.d. (scient.)
Jørgensen, Malene Ryborg (mrj) PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.
Kasper, Christina (ck) Assistant Research Professor, MSc, PhD (pharm.) forsk.adjunkt, cand.scient, ph.d. (pharm.)
Kastrup, Jette Sandholm (jsk) Associate Professor, PhD (pharm.) lektor, cand.pharm., erhvervsforsker
Kristensen, Jørgen Bonefeld Scholarstudent scholarstipendiat, stud.pharm.
Krogsgaard-Larsen, Povl (ano) Rector, Professor, DSc (pharm.) rektor, professor, dr.pharm.
Kæseler, Nina Dürr University Instructor, MSc (pharm.) amanuensis, cand.pharm.
Larsen, Ingrid Kjøller (ikl) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Larsen, Uffe (ul) PhD student, MSc ph.d.-studerende, cand.scient.
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STAFF
Lauritzen, Anette Scholarstudent scholarstipendiat, stud.pharm.
Liljefors, Tommy (tl) Professor, PhD (chemistry) professor, fil.dr.
Lunn, Marie-Louise PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Madsen, Christian (chm) PhD student, MSc ph.d.-studerende, cand.scient.
Madsen, Ulf (um) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Mølgaard, Per (pm) Associate Professor, PhD (agro.) lektor, ph.d. (agro.)
Nielsen, Bettina Bryde (bbn) Assistant Research Professor PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)
Nielsen, Birgitte (bn) Research Assistant, MSc (pharm.) forskningsassistent, cand.pharm.
Nielsen, Mogens (mon) Associate Professor, MSc lektor, cand.scient.
Olsen, Christian Adam (cao) PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.
Olsen, Lotte (lool) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Pawlas, Jan (japa) Assistant Professor, PhD (pharm.) adjunkt, ph.d. (pharm.)
Petersen, Dorte Krehan Seir (dsp) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Petersson Britt (bp) PhD student MSc (pharm.) ph.d.-studerende, cand.pharm.
Poulsen, Anders (ap) PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.
Rønsted, Nina (nir) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Sairafianpour, Majid (msai) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Severinsen, Rune (rs) PhD student, MSc ph.d.-studerende, cand.scient.
Simonsen, Henrik Toft (hts) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Smitt, Ulla Wagner (uws) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Strømgaard, Kristian (krst) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)
Stærk, Dan (ds) Assistant Professor, MSc, PhD (pharm.) adjunkt, cand.scient., ph.d. (pharm.)
Valgeirsson, Jón (jv) PhD student, MSc ph.d.-studerende
Vogensen, Stine Byskov (sv) PhD student, MSc, (pharm.) ph.d.-studerende, cand.pharm.
Wellendorph Petrine (pw) University Instructor, MSc (pharm.) amanuensis, cand.pharm.
Wenckens, Martin (mwe) PhD student, MSc ph.d.-studerende, cand.scient.
Ziegler, Hanne (hz) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Østergaard, Niels PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.
Administrative and technical staff
Allen, Jeanette Cleaner rengøringsassistent
Axkær, Merete Cleaner rengøringsassistent
Brix, Dorte (db) Senior Laboratory Technician laborant, laboratorieoverassistent
Christensen, Peter A. Trainee, Precision Mechanic finmekanikerelev
Christensen, Peter (pc) Laboratory Engineer, Senior Laboratory Technician laboratorietekniker, laboratorieoverassistent
Døring, Heidi L. (hela) Senior Laboratory Technician laborant, laboratorieoverassistent
Eriksen, Anette Lundskov (ale) Senior Laboratory Technician laborant, laboratorieoverassistent
Frederiksen, Anne Lisbeth (alf) Senior Clerk overassistent
Gauguin, Bente (bega) Senior Laboratory Technician laborant, laboratorieoverassistent
Geneser, Ulla (ug) Laboratory Engineer, Senoir Laboratory Technician laboratorietekniker, laboratoriefuldmægtig
Jensen, Kurt Hjælm Cleaner sanitør
Jensen, Frank Stau Trainee, Precision Mechanic finmekanikerelev
Jørgensen, Anders (aj) Web Student Assistant web-studentermedhjælper
Jørgensen, Jan Skov Semi-skilled worker specialarbejder
Keshtkar, Sharareh (shk) Senior Laboratory Technician laborant, laboratorieoverassistent
Klint, Karsten (kk) Assistant Engineer, Precision Mechanic ingeniørassistent, finmekaniker
Krogsgaard-Larsen, Niels Student Assistent studentermedhjælper
Krydsfeldt, Katrine (kakr) Senior Laboratory Technician laborant, laboratorieoverassistent
Lindgreen, Tina (tili) Senior Laboratory Technician laborant, laboratorieoverassistent
Lund, Anne M. Senior Clerk overassistent
Møller, Per Thrane Semi-skilled worker specialarbejder
PAGE 130
ANNUAL REPORT 2000–2001
Ngamrabiab, Uraiwan (ung) Senior Laboratory Technician laborant, laboratorieoverassistent
Nielsen, Anne-Mette (amn) Managing Clerk kontorfuldmægtig
Nordly, Anne (ano) Managing Clerk kontorfuldmægtig
Palmgren-Salomonsson, Lars (lp) Laboratory Porter, Precision Mechanic laboratoriebetjent, finmekaniker
Rad, Shahroz Tavakoli Cleaner rengøringsassistent
Rasmussen, Peter Student Assistant studentermedhjælper
Rønne, Bente Cleaner rengøringsassistent
Simonsen, Birgitte (bsi) Senior Laboratory Engineer laboratorietekniker, laboratorieoverassistent
Sørensen, Lise Baadsgaard (lbs) Senior Laboratory Engineer laboratorietekniker, laboratorieoverassistent
DEPARTMENT OF PHARMACEUTICS
Deparmental Board 2001
Head of Department: Associate Professor Margrethe Rømer Rassing
Deputy Head of Department: Associate Professor Bente Steffansen
Associate Professor Jørn Møller-Sonnergaard
Assistant Engineer Arne Steinicke Jensen
Student Erik Thygesen
Secretariat
Open from: 8.30 A.M. - 3.00 P.M. +45 35 30 62 36
Fax +45 35 30 60 30, 3rd floor
Fax +45 35 30 60 31, 7th floor
Scientific Staff
Email: Initials followed by @dfh.dk.
Adrian, Charlotte (ca) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Bagger, Morten (moba) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Bechgaard, Erik (eb) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Beier, Anne Mette (aho) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Brodin, Birger (bbr) Associate Research Professor, PhD forskningslektor, (lic.scient.)
Christensen, Janne Ørskov (jach) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Christrup, Lona Louring (llc) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Davidsen, Jesper (jeda) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Eriksson, André Huss (ahe) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Foged, Camilla (cfo) PhD student, MSc ph.d.-studerende, cand.scient.
Frederiksen, Kjeldtoft Henrik (hkf) PhD student, Msc (pharm.) ph.d.-studerende, cand.pharm.
Frøkjær, Sven (sf) Professor, PhD, MSc (pharm.) professor, ph.d. (pharm.)
Hansen, Tue (tue) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Heydenreich, Annette Vinther (ava) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Hovgaard, Lars (lh) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Høst, Jan (jaho) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Jacobsen, Jette (jeja) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Johansen, Anita (aj) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Jørgensen, Lene (lej) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Karpf, Ditte Maria (dmk) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Kristensen, Henning Gjelstrup (hgk) Professor, DSc (pharm.) professor, dr.pharm.
Kristensen, Jakob (jk) University Instructor, MSc (pharm.) amanuensis, cand.pharm.
Larsen, Casper Crilles PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
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STAFF
Departmental Board 2002
Head of Department: Associate Professor Lars Hovgaard
Deputy Head of Department: Associate Professor Bente Steffansen
Associate Professor Jørn Møller-Sonnergaard
Assistant Engineer Arne Steinicke Jensen
PhD student Camilla Foged (observer)
Student Jacob Grønne
Lennernäs, Hans Assigned Professor adjungeret professor
Manby, Pedersen Kenneth (kma) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Müllertz, Anette (amu) Associate Professor, PhD, MSc lektor, ph.d. (civ.ing.)
Møller, Horn Eva (ehm) Assistant professor, PhD, MSc adjunkt, ph.d.
Møllmann, Hostrup Susanne (shm) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Møller-Sonnergaard, Jørn (jms) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Nielsen, Carsten Uhd (cun) Assistant professor, MSc (pharm.) adjunkt, cand.pharm.
Nielsen, Hanne Mørck (hmn) Assistant Research Professor, PhD, MSc (pharm.) forskningsadjunkt, ph.d. (pharm.)
Nielsen, Seier Flemming (fsn) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Pedersen, Tina Bjeldskov (tbp) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Petersen, Frederik Jacob (fjp) University Instructor, MSc (pharm.) amanuensis, ph.d.-stud. cand.pharm.
Petersen, Kamilla Buchberg (kbp) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Rasmussen, Mette (mr) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Rassing, Margrethe Rømer (mrr) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Rømsing, Janne (jr) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Schæfer, Torben (ts) Associate Professor, DSc (pharm.) lektor, dr.pharm.
Seo, Anette Elin (aes) PhD student, MSc ph.d.-studerende, m.sc.
Spliid, Henrik ([email protected]) External Associate Professor, PhD (tech.) ekstern lektor, lic.tech.
Steffansen, Bente (bds) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Storm, Gert Assigned Professor adjungeret professor
Ståhl, Kristina (krs) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Sunesen, Vibeke Hougaard (vhj) PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.
Sønderkær, Susanne (suso) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Thomsen, Anne Engelbrecht (anth) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Tjellesen, Lone External Associate Professor ekstern lektor, afdelingslæge, dr.med.
Vermehren, Charlotte (cv) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)
Weert,van de Marco (mvdw) Research Fellow forskningsstipendiat, ph.d. (pharm.)
Wørts, Ole ([email protected]) Assigned Professor adjungeret professor, direktør
Administrative and technical staff
Boldsen, Ida (ida) Senior Laboratory Technician laboratorieoverassistent
Christensen, Malene (mc) Trainee, Laboratory Technician laborantpraktikant
Davidsen, Jytte (jd) Pharmaconomist farmakonom
Dinitzen, Bettina (bedi) Senior Laboratory Technician laboratorieleder
Eltong, Birgitte (biel) Senior Laboratory Technician laboratorieoverassistent
Hannestad, Ove (oh) Laboratory Porter laboratoriebetjent
Hansen, Ruth (ruha) Pharmaconomist farmakonom
Jensen, Arne Steinicke (arje) Assistant Engineer ingeniørassistent
Jensen, Nanni (nj) Senior Clerk overassistent
Jespersen, Lotte (lj) Pharmaconomist farmakonom
Johnsen, Dorrit (dj) Senior Laboratory Technician laboratorieoverassistent
Jørgensen, Liv Cleaner rengøringsassistent
Jørgensen, Claus Cleaner rengøringsassistent
Klausen, Irene (irk) Temporary Lab Technician laborantvikar
Lynge, Sussi Cleaner rengøringsassistent
Nicolajsen, Henning Bo (hbn) Head of Secretariat, MSc (econ.) sekretariatsleder, cand.polit.
Nielsen, Erik (erni) Assistant Engineer ingeniørassistent, elektronikmekaniker
Nielsen, Niels Erik (nen) Assistant Engineer, Precision Mechanic ingeniørassistent, finmekaniker
Pedersen, Ellkier Janne (jep) Pharmaconomist farmakonom
Stevner, Lene (les) Pharmaconomist farmakonom
Sørensen, Marja Leena (mls) Senior Clerk overassistent
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ANNUAL REPORT 2000–2001
Sørensen, Susanne Nørskov (sns) Senior Laboratory Technician laboratorietekniker
Wégens, Birthe (bw) Managing Clerk kontorfuldmægtig
Zhao, Ya Hong Cleaner rengøringsassistent
DEPARTMENT OF PHARMACOLOGY
Departmental Board 2001
Head of Department: Associate Professor, Erik Wind Hansen
Deputy Head of Department: Associate Professor Inger Jansen Olesen
Associate Professor: Klaus Bahl Andersen
Senior Laboratory Technician Jytte Palmgren Salomonsson
Senior Laboratory Technician Gunilla Steven
PhD student Henrik Tang Vestergaard (observer)
Student Anne Zimmermann
Secretariat
Ruth Jensen +45 35 30 63 21
Eva Nielsen +45 35 30 63 29
Fax: +45 35 30 60 20
Scientific Staff
Email: Initials followed by @dfh.dk
Andersen, Klaus Bahl (kba) Associate Professor, PhD lektor, ph.d. (lic.scient.)
Bjerrum, Ole Jannik (ojb) Professor, M.D., D.M. Sci. professor, dr.med.
Christensen, Jens Dencker (jdc) Associate Professor, PhD lektor, ph.d. (lic.pharm.)
Christensen, Lars Harder (lhc) Scholarship Student (pharm.) stud.pharm. scholarstipendiat
Clausen, Rikke (ricl) PhD student, MSc ph.d.-studerende, cand.scient.
Dalsgaard, Grethe Tang (gtd) Research Assistant, MSc (pharm.) forskningsassistent, cand.pharm.
Engberg, Jan (fax: 35 30 60 22) (je) Professor, DSc professor, (dr.scient.)
Erichsen, Helle Kirstein PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Fjalland, Bjarne (bf) Associate Professor, PhD lektor, ph.d. (lic.pharm.)
Frandsen, Aase (aaf) Associate Professor, DSc lektor, dr.scient.
Fuglsang, Anders (anfu) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Gegelashvili, Georgi (gege) Associate Professor, PhD lektor, ph.d.
Hansen, Erik Wind (ewh) Associate Professor, PhD lektor, ph.d. (lic.pharm.)
Hansen, Harald S. (hsh) Associate Professor, DSc docent, dr.scient.
Hansen, Henrik Assistant Research Professor, MSc (pharm.) forskningsadjunkt, cand.pharm.
Hermansen, Keld Veterinary Advisor veterinært tilsyn
Jelic, Katarina (kaje) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Jensen, Liselotte Brix (lbj) PhD student, MSc ph.d.-studerende, cand.scient.
Jensen, Marianne Lerbech PhD student, MSc ph.d.-studerende, cand.scient.
Johansen, Thue PhD student MSc (med.) ph.d.-studerende, cand.med.
Klavsen, Tine (tikl) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Kristiansen, Uffe (uk) Associate Professor, PhD lektor, ph.d. (pharm.)
Kristensen, Anders Skov (ask) PhD student, MSc ph.d.-studerende cand.scient.
Kyhl, Lars Erik Broksøe (lek) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Larsen, Helmer Ring (hrl) Professor, M.D., D.M. Sci. professor, dr.med.
Larsen, Søren Thor PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Larsson, Orla Miller (oml) Associate Professor, PhD lektor, ph.d. (lic.scient.)
Lund, Trine Meldgaard (tml) Associate Professor, PhD lektor, ph.d. (lic.pharm.)
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STAFF
Departmental Board 2002
Head of Department: Associate Professor, Erik Wind Hansen
Deputy Head of Department: Associate Professor Inger Jansen Olesen
Professor Arne Schousboe
Senior Laboratory Technician Jytte Palmgren Salomonsson
Laboratory Porter Teddy Pærremand
PhD student Henrik Tang Vestergaard (observer)
Student Marianne Hald Larsen
Moesby, Lise (lm) Associate Professor, PhD lektor, ph.d. (pharm.)
Moesgaard, Birthe (bm) Assistant Professor, MSc adjunkt, (cand.scient.)
Mortensen, Martin (mamo) PhD student, MSc ph.d.-studerende, cand.scient.
Maach-Møller, Bo External Associate Professor ekstern lektor
Nielsen, Pia Birch (piab) PhD student, MSc (pharm.) ph.d.studerende, cand.pharm.
Olesen, Inger (io) Associate Professor, M.D., D.M. Sci. lektor, dr.med.
Petersen, Gitte (gipe) University Instructur, MSc (pharm.) amanuensis, cand.pharm.
Petersen, Karina PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Pickering, Darryl (picker) Associate Professor, PhD lektor, ph.d.
Poulsen, Claus Fog (cfp) PhD student, MSc ph.d.-studerende, cand.scient.
Rasmussen, Søren External Associate Professor ekstern lektor
Riise, Erik S. (esr) Associate Professor lektor, ph.d. (scient.)
Sarup, Alan (asa) Research Assistant, MSc (pharm.) forskningsassistent (cand.pharm.)
Schousboe, Arne (fax: 35 30 60 21) (as) Professor, DSc professor, dr.scient.
Sheykhzade, Majid (mash) Assistant Professor, MSc (pharm.) adjunkt, ph.d.
Sveigaard, Helle H. PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Thygesen, Peter External Associate Professor ekstern lektor
Vestergaard, Henrik Tang (htv) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Waagepetersen, Helle Sønderby (hsw) Assistant Research Professor, PhD forskningsadjunkt
Zedeler, Anne (az) PhD student, MSc ph.d.studerende, cand.scient.
Zinck, Tina (tzi) PhD student, MSc ph.d.studerende, cand.scient.
Teaching Assistants
Jesper Drøgemüller
Administative and technical staff
Bonnichsen, Michael (mibo) Laboratory Porter/keeper laboratoriebetjent/dyrepasser
Busk, Kirsten Aagaard (kab) Senior Laboratory Technician laboratorieoverassistent
Bötkjær, Anja Student Assistant studentermedhjælp
Colding, Janne Møgelhøj (jco) Laboratory Engineer laboratorietekniker
Danø, Hanne (hd) Managing Clerk kontorfuldmægtig
Dyhrfjeld, Helle (hdy) Substitute Laboratory Engineer laboratorieteknikervikar
Hansen, Helle Dupont (hdh) Cleaner rengøringsassistent
Hansen, Ruth (ruh) Cleaner rengøringsassistent
Hedeman, Sanne S. (sahe) Senior Laboratory Technician laboratorieoverassistent
Helbo, Anders (ahelbo) EDP Student Assistant EDB studentermedhjælp
Jensen, Bettina (beje) Laboratory Porter/keeper laboratoriebetjent/dyrepasser
Jensen, Randi (rje) Senior Laboratory Technician laboratorieoverassistent
Jensen, Ruth (rj) Senior Clerk overassistent
Krogsriis, Anne-Mette Laboratory Technician laborant
Lynggaard, Katrine Riis (krl) Cleaner rengøringsassistent
Metz, Kirsten (kme) Senior Laboratory Technician laboratorieoverassistent
Michäely, Marianne (mami) Laboratory Engineer laboratorietekniker
Nielsen, Eva (en) Senior Clerk overassistent
Palmgren, Jytte S. (jps) Senior Laboratory Technician laboratorieoverassistent
Petersen, Lone (lope) Laboratory Engineer laboratorietekniker
Petersen, Rudy (rpe) Cleaner rengøringsassistent
Pærremand, Teddy (tp) Laboratory Porter laboratoriebetjent
Rützou, Cathrine Student Assistant studentermedhjælp
Schøler, Betina (bsc) Laboratory Engineer laboratorietekniker
Steven, Gunilla (gs) Senior Laboratory Technician laboratorieoverassistent
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ANNUAL REPORT 2000–2001
Strynbo, Marianne (ms) Assistant assistent
Søndergaard, Robert (rsn) Trainee, Laboratory Technician laborantelev
Sørensen, Grete (grs) Senior Laboratory Technician laboratorieoverassistent
Thuesen, Kirsten (kit) Laboratory Engineer laboratorietekniker
Voss, Jeppe Student Assistant studentermedhjælp
DEPARTMENT OF SOCIAL PHARMACY
Departmental Board 2001
Head of Department: Associate Professor Poul R. Kruse
Deputy Head of Department: Professor Ebba Holme Hansen
Associate Professor Janine M. Morgall Traulsen
Managing Clerk Jytte Sørensen
PhD student Kristin Eskildsen (observer)
Student Helle Poulsen
Secretariat
9.00 am - 3.30 pm
Tel.: +45 35 30 63 44 / +45 35 30 63 50 / +45 35 30 62 23
Fax: +45 35 30 60 50
Scientific staff
Email: Initials followed by @dfh.dk
Christensen, Søren Troels (stc) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)
Clausen, Jørgen External Associate Professor, PhD, MSc (econ.) ekstern lektor, ph.d., cand.oecon.
Eskildsen, Kristin (kres) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Hansen, Ebba Holme (ehh) Professor, MSc (pharm.) professor, cand.pharm.
Hansen, Kim Haugbølle External Associate Professor, PhD, MSc (eng.), BSc (pol.sc.) ekstern lektor, ph.d., cand.polyt.
Haugbølle, Lotte Stig (lsh) Associate Professor PhD (pharm.) lektor, ph.d. (pharm.)
Hopp, Trine (trh) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Jensen, Thomas Clemens, (thcj) University Instructor, MSc (pharm.) amanuensis, cand.pharm.
Karkee, Shiba PhD student, MSc (clin. pharmacol.) ph.d.-studerende, MSc (clin.pharmacol.)
Knudsen, Pia (pini) Assistant Professor PhD (pharm.) adjunkt, ph.d. (pharm.)
Kruse, Poul R. (pk) Associate Professor, DSc (pharm.) lektor, dr.pharm.
Larsen, Jakob Bjerg (jbl) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Launsø, Laila (ll) Associate Professor, DSc (sociology) lektor, dr.scient.soc.
Mishra, Pranaya PhD student, MSc (clin.pharmacol.) ph.d.-studerende, M.Sc. (clin.pharmacol.)
Møldrup, Claus (cm) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)
Nielsen, Merete W. (mwn) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Rossing, Charlotte (chan) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Rüdinger, Bertel (br) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.
Sørensen, Ellen Westh (ews) Associate Professor, MSc (pharm.) lektor, cand.pharm.
Trap, Birna PhD student, MSc (pharm.), BCom ph.d.-studerende, cand.pharm., HD
Traulsen, Janine M. Morgall (jam) Associate Professor, PhD (sociology) lektor, fil.dr.
Administative and technical staff
Andersen, Gunhild (ga) Clerk, Cleaner kontorassistent, rengøringsassistent
Jensen, Anne Blem (abj) Senior Clerk, Language Secretary overassistent, korrespondent
Nørgaard, Jette (jen) Senior Clerk, Language Secretary overassistent, korrespondent
Sørensen, Jytte (js) Managing Clerk, BCom kontorfuldmægtig, merkonom
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Departmental Board 2002
On leave: Head of Department: Associate Professor Lotte Stig Haugbølle
Acting Head of Department: Professor Ebba Holme Hansen
Acting Deputy Head of Department: Associate Professor Claus Møldrup
Senior Clerk Anne Blem Jensen
PhD student Kristin Eskildsen (observer)
Student Anders Helbo
ANNUAL REPORT 2000–2001
THE DANISH PHARMACEUTICAL LIBRARY
Phone: + 45 35 30 63 19
Fax: + 45 35 30 60 60
Opening Hours:
Monday – Thursday: 9 - 16; Friday 10 - 15.30
Check opening hours in July and August
Information:
Circulation desk + 45 35 30 63 19
Information desk + 45 35 30 64 60
E-mail: [email protected]
Library Board
Alice Nørhede, The Library
Annemette Møller Hansen, The Library
Søren Brøgger Christensen, Department of Medicinal Chemistry
Orla Miller Larsson, Department of Pharmacology
Margrethe Rømer Rassing, Department of Pharmacy
Erling Sonnich Thomsen, Department of Analytical and Pharmaceutical Chemistry
Ellen Westh Sørensen, Department of Social Pharmacy
Henrik Parshad, PhD Department of Pharmacy
Marianne Hald Larsen, student
Anne Zimmermann, student
Staff
E-mail: Initials followed by @dfh.dk
Bladt, Birgitte Ruste (brb) Clerk assistent
Hald, Niels Peter Krogh Student Assistant studentermedhjælp
Hansen, Annemette Møller (amh) Research Librarian, MSc (pharm.) forskningsbibliotekar, cand.pharm.
Keller, Marianne (mk) Librarian bibliotekar
Kaad, Lene (leka) Librarian bibliotekar
Munck, Jesper (jemu) Information Officer, MA informationsmedarbejder, cand.mag.
Nørhede, Alice (aln) Head of Library Service biblioteksleder
Overgaard, Ole (olo) Library Porter biblioteksbetjent
Petersen, Filip Hetmar Cleaner rengøringsassistent
Thiesen, Lis (lt) Senior Clerk overassistent
Weile, Martin (mw) Librarian bibliotekar
PAGE 136
ADMINISTRATION DEPARTMENT
Opening hours:
Monday – Thursday 8.30 - 16; Friday 8.30 - 15.30
Phone: +45 35 30 60 00
Fax: +45 35 30 60 01
E-mail: Initials followed by @dfh.dk
HEADS OF SCHOOL
Rector:
Povl Krogsgaard-Larsen (rektor) Professor, DSc (pharm.) professor, dr.pharm.
Deputy Rector:
Bjarne Fjalland (bf) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)
Administrator
Judith Christiansen (jc) MA cand.mag.
Security officer
Johansen, Jørgen Stage (jsj) Laboratory Engineer laboratorietekniker
Personnel department
Almegaard, Tine (ta) Administrative Officer, LLB fuldmægtig, cand.jur.
Gindeberg, Marianne (magi) Senior Clerk overassistent
Hansen, Tina Senn (tsh) Senior Clerk overassistent
Jensen, Anni Kølner (akj) Senior Clerk, Receptionist overassistent, receptionen
Knudsen, Tage Ø. (tk) Head Porter betjentformand
Langhoff, Birgit (bila) Senior Clerk overassistent
Pedersen, Susanne (sp) Senior Clerk overassistent
Riis, Elisabeth (elri) Head of Secretariat, LLB sekretariatschef, cand.jur.
Sørensen, Anne (ans) Senior Clerk overassistent
Tribe, Louise (ltr) Administrative Officer, LLB fuldmægtig, cand.jur.
Course administration
Fjalland, Ilse (if) Registrar, MSc (pharm.) studiechef, cand.pharm.
Flarup, Malene (mf) Office Trainee kontorelev
Jørgensen, Marianne W. (mwj) Administrative Officer, BcomInt fuldmægtig, cand.merc.int.
Laursen, Inge Debois (idl) Administrative Officer, MSc (pharm.) fuldmægtig, cand.pharm.
Ottosen, Susanne (sus) Managing Clerk kontorfuldmægtig
Sjelle, Pia (pia) Senior Clerk overassistent
Ulriksen, Gitte Metz (gmu) Senior Clerk overassistent
Vester-Andersen, Lærke (lva) Administrative Office,r MSc (pharm.) fuldmægtig, cand.pharm.
Wiese, Lone (lw) Senior Clerk overassistent
Course guidance
Dahl, Christoffer (cdl) Student Counsellor, pharmacy student studievejleder, stud.pharm.
Kendra, Jimmy (jik) Student Counsellor, pharmacy student studievejleder, stud.pharm.
Koch, Bettina (beko) Student Counsellor, pharmacy student studievejleder, stud.pharm.
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Finance department
Andersen, Dorthe (doan) Senior Clerk overassistent
Bernhard, Rikke (rbj) Senior Clerk overassistent
Christiansen, Anja (ac) Office Trainee kontorelev
Freidal, Manon (mf) Senior Clerk overassistent
Haugan, Britta (bh) Managing Clerk kontorfuldmægtig
Jensen, Ann-Mari Østergaard (amj) Senior Clerk overassistent
Jensen, Villy Dahl (vdj) Finance Manager, BSc (econ.) økonomichef, cand.scient.pol.
Jørgensen, Tina Lund (tlj) Clerk assistent (+ DSR)
Knudsen, Flemming Siggaard (fsk) Managing Clerk fuldmægtig
Higher education administration system (STADS)
Borgholm, Birthe (bb) Electronic Data Consultant, MSc edbkonsulent, cand.scient.
Web
Korzen, Henrik (heko) Webmaster webmaster
IT department
Andersen, Jesper Stemann (jsa) Student Assistant studentermedhjælp
Aunfelt, Karsten (kau) System Administrator systemadministrator
Hossein, Ehsani (hoeh) Electronic Data Assistant, Engineer edb-tekniker, ingeniør
Szymanski, Thomas (tsz) Student Assistant studentermedhjælp
Sørensen, Jørn Bo (jbs) Head of IT IT-leder
Technical services
Christensen, Tom Mechanic maskinarbejder
Olsen, Allan (alol) Mechanic maskinarbejder
Olsen, Freddy Technical Assistant specialarbejder
Petersen, John (jop) Engineer maskinmester
Building administration
Bender, Allan Porter betjent
Harder, Ronald (roha) Porter betjent
Knudsen, Tage Ø. (tk) Head Porter betjentformand, portner
Rasmussen, Kjeld (kjr) Building Administrator bygningsforvalter
PAGE 138
ANNUAL REPORT 2000–2001
Danmarks Farmaceutiske Højskole
Universitetsparken 2
2100 København Ø
Telefon: 35 30 60 00
Fax: 35 30 60 01
E-mail: [email protected]
Internet: www.dfh.dk