abbreviation: PBPK · full name: physiologically based pharmacokinetic model
A mathematical framework that describes drug absorption, distribution, metabolism, and excretion using actual physiological parameters — organ volumes, blood flows, enzyme abundances, and tissue partitioning — rather than empirical compartments. PBPK models enable prospective predictions for special populations, drug interactions, and paediatric dosing, and are accepted by FDA and EMA for regulatory submissions.
PBPK modeling (physiologically-based pharmacokinetic modeling) has become an indispensable tool in modern drug development. Unlike empirical compartmental models, PBPK models integrate actual physiological parameters — organ volumes, blood flows, enzyme abundances, and transporter expression — with drug-specific properties to predict concentration-time profiles in plasma and tissues.
The FDA PBPK Guidance for Industry outlines the format and content requirements for PBPK analyses submitted in regulatory applications. A primary use case is drug-drug interaction prediction: PBPK models can simulate the effect of CYP inhibitors and inducers on a new drug's exposure, potentially replacing costly clinical DDI studies. The EMA Guideline on the Investigation of Drug Interactions similarly accepts qualified PBPK models for DDI risk assessment.
Beyond DDI prediction, PBPK modeling supports dose recommendations in special populations (hepatic impairment, renal impairment, paediatrics, pregnancy), food-effect predictions, and formulation bridging. The three major software platforms — Simcyp (Certara), GastroPlus (Simulations Plus), and PK-Sim (Open Systems Pharmacology) — each offer validated physiological databases and have regulatory precedent. PubMed literature on PBPK applications: PubMed PBPK research.