Physiologically based pharmacokinetic and toxicokinetic modeling: A multidisciplinary approach to drug development and ecotoxicology

Introduction: Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool in pharmaceutical research and drug development, offering accurate predictions of drug absorption, distribution, metabolism, and elimination (ADME). This method, when extended to xenobiotics, enables the study of toxins and other substances through physiologically based toxicokinetic (PBPT) models. Methodology: This narrative review outlines recent applications of PBPK and PBTK modeling in drug development and ecotoxicology, based on literature retrieved from PubMed, Scopus, and Web of Science. Topic: By incorporating physiological and biochemical data, PBPK models provide more precise simulations that closely resemble in vivo conditions. Advances in technology have improved the feasibility of these models, making them increasingly valuable for predicting drug behavior, as well as for cross-species and route-of-administration extrapolation. The mechanistic nature supports regulatory decision-making and reduces the need for extensive in vivo testing. Furthermore, PBPK models are instrumental in special population assessments, such as pediatrics or patients with organ impairment. Conclusion: With continued integration of in silico tools and data obtained by other testing, PBPK modeling is poised to become a central platform in translational pharmacology and safety assessment. Regulatory agencies most commonly use PBPK models to support the assessment and prediction of drug-drug interactions.