Clinical Pharmacology – Chemical
When dosing drugs to patients it is essential to have good understanding of drug safety and efficacy in various subgroups of patients rather than an average person. Expectation of extreme effects, side effects or lack of therapeutic effects in some subgroups following administration of similar doses requires full understanding of variability and the importance of identifying covariates that determine the exposure to the drug candidates in each individual.
Developing population based Physiologically-based Pharmacokinetics (PBPK) models where such covariates are mechanistically incorporated can assist with predicting between and within subjects variability. The key element of this approach is the separation of information on the system (i.e. human body) from that of the drug (e.g. physicochemical or metabolism parameters) and the study design (e.g. dose, route and frequency of administration, concomitant drugs and food). We have made great progress in identifying covariates affecting inter-subject variability, however our understanding of factors affecting intra-subject variability is still limited. In the presentation, the recent advancements and knowledge gaps in determining inter- and intra-subject variability in PBPK modelling are discussed.