Quantitative and Systems Pharmacology Approaches for the Development of Oncology Drugs

Modelling and simulation of the absorption, distribution, metabolism and elimination (ADME) of a drug, using a mechanistic approach, can help to predict the potential exposure of a drug at a given dose in the population of interest. The development of in vitro – in vivo extrapolation (IVIVE) relating to ADME to predict pharmacokinetic (PK) parameters and drug-drug interactions (DDIs) has accelerated over the past decade. Application of IVIVE with physiologically based pharmacokinetic (PBPK) modelling to characterize PK and potential DDIs is being used increasingly within the pharmaceutical industry. Furthermore, guidance documents assessing the DDI potential of drugs were recently updated by the FDA and the EMA; both agencies advocated the use of PBPK modelling. The development of a PBPK model for special populations, including oncology patients will be discussed during the presentation. In addition, examples of PBPK modelling using the Simcyp Simulator for small molecules will also be presented.