Pharmacokinetic–pharmacodynamics Modeling in Modern Drug Development

Pharmacokinetic–pharmacodynamic (PK–PD) modelling is now a foundational tool in modern drug development, linking drug exposure to pharmacologic response to aid dose optimisation, efficacy, and safety. By integrating pharmacokinetics (absorption, distribution, metabolism, excretion) with pharmacodynamics (receptor-binding, dose–response, mechanistic signalling), PK–PD models enable data-driven decision-making in preclinical and clinical phases. Mechanism-based and population PK–PD approaches—including physiologically based (PBPK) and target‐mediated disposition models—allow prediction across species, disease states, and subpopulations. Regulatory agencies such as the U.S. FDA and EMA recognize model-informed drug development (MIDD) as key to trial design, dose selection and approval. Emerging advances—including artificial intelligence, quantitative systems pharmacology (QSP), and real-world data integration—are enhancing model predictive power and supporting precision medicine. This review discusses current methodologies, applications, regulatory perspectives, and future directions in PK–PD modelling, underlining its role in accelerating efficient, patient-centered drug development.