pharmacokinetics (pk) ®the study of the disposition of a drug ®the disposition of a drug includes...
TRANSCRIPT
Pharmacokinetics (PK)
The study of the disposition of a drugThe disposition of a drug includes the
processes of ADME - AbsorptionDistributionMetabolismExcretion Elimination
Importance
Without the knowledge gained from PK studies, patients may suffer:Toxic drugs may accumulateUseful drugs may have no benefit
because doses are too small to establish therapy
A drug can be rapidly metabolized.
Routes Of Administration
Routes Of Drug Administration
EnteralParenteral
OralInjection RectalRespiratoryTopical
Absorption
The passage of drug from the site of administration into the general circulation.
Exception: Intravenous injectionsI.V Drug Oral Drug
Immediately Delayed
completely incomplete
Absorption relies on Passage through membranes to reach
the blood passive diffusion of lipid soluble species.
The Process
Absorption & Ionization
Non-ionised drug
More lipid soluble drug
Diffuse across cell membranes more
easily
Most drugs are absorbed in the small intestine, because It is the portal for absorption of
nutrients into blood It is surrounded by a very thin
membrane with a large surface area
Site Of Absorption
Rate & Extent
Rate - How rapidly does the drug get from its site of administration, to the general circulation?
Extent - How much of the administered dose enters the general circulation
Plasma Protein Binding
Many drugs bind to plasma proteins in the blood steam
Plasma protein binding limits distribution.A drug that binds plasma protein diffuses
less efficiently, than a drug that doesn’t.
Elimination
The irreversible removal of the parent drugs from the body
Elimination
Drug Metabolism (Biotransformation)
Excretion
Drug Metabolism
The chemical modification of drugs with the overall goal of getting rid of the drug
Enzymes are typically involved in metabolism
DrugMetabolism More polar
(water soluble)Drug
Excretion
Sites of Drug Metabolism
Metabolism occurs in many tissuesE.g. brain, kidney, lungBut mostly in the liver because …
all of the blood in the body passes through the liver.
Consequences Of Metabolism
Drug metabolism != Drug inactivationThe metabolite may have
Equal activity to the drug No or reduced activity Increased activity (Prodrugs) Toxic properties, not seen with the parent
drug
The Most Important Enzymes
Microsomal cytochrome P450 monooxygenase family of enzymes, which oxidize drugs
Act on structurally unrelated drugsMetabolize the widest range of drugs.
Excretion
The main process that body eliminates "unwanted" substances.
Most common route - biliary or renal Other routes - lung (through
exhalation), skin (through perspiration) etc.
Lipophylic drugs may require several metabolism steps before they are excreted
Pharmacodynamics (PD)
The study of the biochemical and physiological effects of drugs.
Pharmacokinetics
Pharmacodynamics
what the body does to the drug
what the drug does to the body.
Drug Interaction
When a drug alters the effects of another drug
Drug A may alter these factors of drug B: Efficiency Rate of effect Side effects.
Drug Interaction
Pharmacokinetic:
Amount of drug in blood is altered
Pharmacodynamic:
The drug effect is altered
References
A First Course in Pharmacokinetics and Biopharmaceutics - available at http://www.boomer.org/c/p1/
http://www.le.ac.uk/pa/msc/pklecture.pdf http://web.vet.cornell.edu/public/pharmacokinetics/
pharmacokinetics.html The Liver and Drug Metabolism - available at
http://adultpain.nursing.uiowa.edu/MedGen/Liver.htm http://www.ttuhsc.edu/pharm/Freeman/med/DrugElim1.ppt http://www.bps.ac.uk/epharnet/adme.ppt http://www.usask.ca/medicine/pharmacology/
Mon11SEP.pdf http://www.usask.ca/medicine/pharmacology/Fri08SEP.pdf