‘Middle-Out'–Joined-Up Thinking For Pharmacokinetic–Pharmacodynamic Model-Based Learning And Confirming In Drug Development

By Geoff Tucker

Emeritus Professor of Clinical Pharmacology, University of Sheffield, UK; Vice President of Translational Sciences (Certara); Head of Consultancy (Simcyp (Certara)); and Chair of the Board of Pharmaceutical Sciences, International Pharmaceutical Federation.

Modeling and simulation have finally come of age in the processes of new drug development and regulation. An integral part of this realization is the increasing application of pharmacokinetic-pharmacodynamic modeling (PKPD), where PK and PD refer to the mathematical description and prediction of what the body does to the drug and what the drug does to the body, respectively. However, there are fundamentally two camps in PKPD modeling, representing ‘bottom-up’ and ‘top-down’ approaches. The former emphasizes a biological viewpoint while the latter has a strong statistical (pharmacometric) basis.