PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODELING: A TRANSFORMATIVE TOOL IN MODERN BIOPHARMACEUTICS

By transitioning from empirical pharmacokinetic techniques to mechanistic, physiology-driven simulations of drug disposition, physiologically based pharmacokinetic (PBPK) modelling has become a revolutionary approach in drug development. Although exposure metrics are provided by traditional methods like non-compartmental analysis and classical compartment models, their lack of structural biological relevance limits their capacity to forecast performance across various patient groups or formulation modifications. To mechanistically predict absorption, distribution, metabolism, and excretion (ADME) under a variety of conditions, PBPK models integrate anatomical, physiological, and biochemical parameters such as tissue perfusion, organ-specific metabolism, transporter activity, and physicochemical properties. Their use in biopharmaceutics keeps growing, allowing for virtual clinical trial simulations, formulation optimisation, in vitro–in vivo extrapolation (IVIVE), and bioavailability/bioequivalency prediction (BA/BE). By enhancing first-in-human (FIH) dose selection, lowering the burden of clinical studies for drug-drug interactions and special population assessments, and providing information for regulatory submissions to organisations like the FDA and EMA, PBPK promotes model-informed drug development. Accuracy is further improved and individualised dosing strategies are supported by recent developments like mechanistic absorption modelling, transporter-based predictions, and integration with machine-learning and omics datasets. In addition to highlighting regulatory case studies, this review summarises fundamental PBPK principles, data requirements, and workflows. It also addresses present issues and potential future developments in bolstering PBPK adoption as a key tool in contemporary biopharmaceutics and precision pharmacokinetics.