Applications of PBPK Modeling and Simulations in The Clinical Pharmacology Field: Lessons from Several Case Studies

Abstract

The utilization of a physiologically-based pharmacokinetic (PBPK) model has become prevalent, especially in drug development by pharmaceutical companies. The regulatory agencies in the US and Europe have already issued guidelines while the Japanese agency is preparing one to support the process. To some extent, applications of PBPK modeling to assess the risk of drug-drug interaction have mainly been discussed. It has been limited to discussing other utilizations such as: 1) conducting a virtual bioequivalence study for a new formulation; 2) assessing PK changes in a Japanese population; and 3) predicting PK profiles of drugs or drug candidates in pediatric subjects. The purpose of this paper is to discuss the current status and future challenges of potential utilizations of PBPK modeling through actual practices and to share regulatory experiences on PBPK modeling in Japan. We summarize the discussions on prospects from the perspective of industry, academia, regulatory agencies, and hospitals.