Physiologically based pharmacokinetic modeling in obesity: applications and challenges

INTRODUCTION: Rising global obesity rates pose a threat to people's health. Obesity causes a series of pathophysiologic changes, making the response of patients with obesity to drugs different from that of nonobese, thus affecting the treatment efficacy and even leading to adverse events. Therefore, understanding obesity's effects on pharmacokinetics is essential for the rational use of drugs in patients with obesity. AREAS COVERED: Articles related to physiologically based pharmacokinetic (PBPK) modeling in patients with obesity from inception to October 2023 were searched in PubMed, Embase, Web of Science and the Cochrane Library. This review outlines PBPK modeling applications in exploring factors influencing obesity's effects on pharmacokinetics, guiding clinical drug development and evaluating and optimizing clinical use of drugs in patients with obesity. EXPERT OPINION: Obesity-induced pathophysiologic alterations impact drug pharmacokinetics and drug-drug interactions (DDIs), altering drug exposure. However, there is a lack of universal body size indices or quantitative pharmacology models to predict the optimal for the patients with obesity. Therefore, dosage regimens for patients with obesity must consider individual physiological and biochemical information, and clinically individualize therapeutic drug monitoring for highly variable drugs to ensure effective drug dosing and avoid adverse effects.