Capillary microsampling in mice: effective way to move from sparse sampling to serial sampling in pharmacokinetics profiling

Abstract

Pharmacokinetic studies are an integral part of drug discovery and development. Mice are the commonly used species for pharmacokinetics studies during early discovery studies. Conventionally, composite PK profiles are obtained from mice studies due to the physiological limitations of the total blood volume that can be drawn over a certain period.With advancements in bioanalytical instrumentation and in blood sampling techniques, analysis with small volume (<50 µL) became feasible enabling serial blood sampling from the mouse for PK studies. The objective of the current study was to develop and establish a serial blood sampling technique in mouse and compare it with the conventional sparse sampling method (composite PK) following oral administration of widely used NSAIDs, diclofenac, celecoxib and tenoxicam, into Swiss Albino mice.The pharmacokinetic parameters of all three probe drugs by serial blood sampling were comparable with that of sparse sampling method. There was no significant difference between the whole blood concentration time profiles of all three drugs between serial sampling and sparse sampling suggesting serial blood sampling method can be easily implemented for mice PK studies.Serial blood sampling technique requires use of fewer number of animals, less quantity of test compound and reduces the possible dosing errors as fewer number of animals need to be dosed resulting in quality PK data and enabling comparison of inter-animal differences in PK profile.