2001
   Basel, Switzerland

Sensitivity Analysis of PBPK and PK/PD Models

Ivan Nestorov

Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK

The undisputed importance of sensitivity analysis (SA) in the modelling practices arises both from the valuable information its results provide and from the universal presence of uncertainty and variability in the real word. The purpose of the current presentation is to show an approach to the structural sensitivity analysis of PK and PD systems, based on three well-known rules in System Theory – the serial connection, the parallel connection and the feedback sensitivity rule. This approach leads naturally to the ranking of the model components with respect to their influence on the system dynamics. The implementation of the approach to the SA of typical PK model structures – the largely parallel mammilary PBPK model and the serial PK/PD model – leads to interesting practical conclusions.