WELAB BARCELONA

Screening Pharmacokinetic assay in the mouse

Aim: To characterize the pharmacokinetics of test compound in the mouse after single oral or intravenous 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.

Screening pharmacokinetics in the mouse is conducted after single dose administration of the compound by the selected route and vehicle. At time points defined previously, two blood samples are withdrawn from each animal. After centrifugation and protein precipitation, compound is determined in plasma by UPLC-MS/MS.

Compound requirement: 15 mg

Turnaround time: 3 weeks 

Experimental design:

– Dose and route: 10 mg/kg (oral gavage) and 1 mg/kg (intravenous injection) (both variable on request)
– Animals: 8 mice / route
– Vehicle: 0.1% Tween 80 and 0.5% hydroxypropyl methylcellulose (oral), variable for intravenous dosing
– Samples: two blood samples from each animal at preset times (8 sampling times up to 24 h / route)
– Replicates: 2 mice / sampling time
– Analytical method: UPLC-MS/MS quantification in plasma after blood centrifugation and protein precipitation using a calibration curve

Delivered results:

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

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