Application of population pharmacokinetics for preclinical safety and efficacy studies

Abstract

From the beginning of the 1980s, population PK has been primarily used in clinical development and only in the last decade has it been convincingly applied in a preclinical setting. Sparse sampling and covariate analyses are key features of preclinical popPK, useful for toxicology and efficacy studies in animals to assemble data obtained from different studies; for describing individual PK and PD; for building mechanistic models; and for performing interspecies scaling-up of disposition and efficacy. Application in disease models, mainly in behavioral and neurological models, allows the quantitative description of PK and PD without frequent blood sampling and recurrent physiological measurements, which are the critical and compromising perturbations of experimental systems. A preclinical population approach to PK and PD, by its versatility and possibility of simulating ‘what if’ scenarios, offers a unique and potent tool in the development of new drugs, in particular biologics.