Physiologically based pharmacokinetics: Advancing the clinical dimension
Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, U.K.
For many years a predominantly academic subject, the application of physiologically-based pharmacokinetic modeling (PBPK) is coming of age in drug development and regulation, reflecting significant advances in recent years in the predictability of key PK parameters from a combination of human in vitro data, drug physicochemical information, and the availability of dedicated software platforms and associated data bases. The complexity of the resulting model depends on the intended application. PBPK is now helping to predict the first-in-human PK, and has the facility to be updated in the light of Phase 1 data. Some of the specific advances and contemporary challenges with respect to predicting the quantitative extent of PK-based drug-drug interactions and the impact of age, genetics, disease and formulation are considered. Also considered are the capability in selecting and designing appropriate clinical studies and its implications for resource-sparing and a more holistic view across the pre-clinical/clinical divide are considered.