Screening Pharmacokinetic assay in rodents

Aim: To characterize the pharmacokinetics of test compound in rodents after single dose administration.

Background information:

Pharmacokinetics is the study of changes in drug concentration over time as a result of the ADME procesess that occur in the body after drug administration (Absorption, Distribution, Metabolism and Excretion). During the Drug Discovery process, new synthetised candidates with an optimum pharmacokinetic profile in rodents are screened for further characterization. In later stages, changes of pharmacokinetics with dose, food, route of administration and sex can be evaluated.

Pharmacokinetics in rodents is conducted after single dose administration of the compound by the selected route and vehicle. At time points defined previously, blood samples are withdrawn from each animal. Upon centrifugation, compound is determined in plasma by UPLC-MS/MS after previous sample treatment (protein precipitation or solid phase extraction).

Experimental design:

  • Screening pharmacokinetic assay in the rat
  • Screening pharmacokinetic assay in the mouse
  • Other pharmacokinetic assays in rodents
  • Route of administration: e.g. oral, intravenous, intraperitoneal, subcutaneous
  • Vehicle: dependent on the route of administration, e.g. 0.1% Tween 80 and 0.5% hydroxypropyl methylcellulose for oral dosing
  • Species, sex, dose, food, replicates per sampling time: dependent on request
  • Analytical method: UPLC-MS/MS quantification in plasma after blood centrifugation using a calibration curve

Delivered results:

  • Plasma concentration-time curves
  • Standard pharmacokinetic parameters determined by non-compartmental analysis