advantages of conducting a stand-alone respiratory safety pharmacology study
Post on 14-Jan-2016
54 Views
Preview:
DESCRIPTION
TRANSCRIPT
Advantages of Conducting a Stand-Alone Respiratory Safety Pharmacology Study
Dennis J. Murphy, PhD, DABT
Director - Safety Pharmacology US
GlaxoSmithKline Pharmaceuticals
Advantages Ventilatory measurements in animal models can be highly variable due
primarily to a sensitivity to environmental changes (stimuli)– Stimuli include noise, odor, movement, handling, light, temperature– As such, measurements require a highly controlled environment for
accurate and repeatable measurements This can be achieved in a stand-alone study Very difficult to achieve in a typical toxicology study where many activities are
constantly ongoing and high number of animals are involved
Stand-alone studies allow the use of animals with a telemetry implant for measuring body temperature and pleural pressure (required to obtain a direct measure of airway resistance)
– Generally not acceptable in a toxicology study due to pathology complications and resource limitations
Advantages (continued) Stand-alone studies have greater flexibility in study design
– Can use either crossover designs (animals serve as their own control) or parallel design with n = 6-8 of single sex per dose group
– Can include recovery time for assessing reversibility or delayed effects (beyond 24 hrs post dose)
– A typical 2/4 week toxicology study can be limited to a parallel design with n=3/sex per dose group (non-rodent) (sufficient for statistical analysis?) and may not include a recovery period (rodent or non-rodent)
Acute (day 1) measurements can be obtained with stand-alone studies– Day 1 measurements are critical because of tachyphylaxis or
tolerance/compensation that can develop on repeat dosing– This can be difficult in toxicology studies because of TK analysis and
enhanced clinical observations that need to be conducted on day1
top related