The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data

Abstract

Comprehensive retrospective approaches in which the abilities of several methods by which human pharmacokinetic parameters are predicted from preclinical pharmacokinetic data and/or in vitro metabolism data were reviewed.The prediction methods reviewed included those methods from scientific literatures.The prediction of main human pharmacokinetics parameters includes clearance(CL),volume of distribution(V_d),half life(t_(1/2)) and bioavailability using allometric scaling,animal-human proportionality,molecular structural parameters,physicochemical measurements,metabolism data in vitro.Such approaches should find utility in the drug discovery and development processes in the identification and selection of compounds that will possess appropriate pharmacokinetic characteristics in humans for progression to clinical trials.