Objectives: The objective of this review was to provide an overview of pharmacokinetic/pharmacodynamic (PK/PD) models, focusing on drug-specific PK/PD models and highlighting their value added in drug development and regulatory decision-making.
Key findings: Many PK/PD models, with varying degrees of complexity and physiological understanding have been developed to evaluate the safety and efficacy of drug products. In special populations (e.g. paediatrics), in cases where there is genetic polymorphism and in other instances where therapeutic outcomes are not well described solely by PK metrics, the implementation of PK/PD models is crucial to assure the desired clinical outcome. Since dissociation between the pharmacokinetic and pharmacodynamic profiles is often observed, it is proposed that physiologically based pharmacokinetic and PK/PD models be given more weight by regulatory authorities when assessing the therapeutic equivalence of drug products.
Summary: Modelling and simulation approaches already play an important role in drug development. While slowly moving away from 'one-size fits all' PK methodologies to assess therapeutic outcomes, further work is required to increase confidence in PK/PD models in translatability and prediction of various clinical scenarios to encourage more widespread implementation in regulatory decision-making.
Keywords: drug development; modelling and simulation; pharmacokinetics/pharmacodynamics; regulatory science; therapeutic equivalence.
© 2019 Royal Pharmaceutical Society.