Pharmacokinetics, modeling, and simulation in the development of sunitinib malate: A case study

Abstract

Pharmacokinetics, modeling, and simulation are integral components of the drug development process, with potential impact on the regulatory approval process and approval language, as well as the clinical use of the drug. The US Food and Drug Administration and other regulatory agencies recommend inclusion of such analyses as part of the regulatory submission process. The pharmacokinetics, modeling, and simulation studies performed for the anticancer agent sunitinib malate are presented here as a case study. Population based pharmacokinetic and pharmacokinetic-pharmacodynamic studies supported the sunitinib dosing schedule in the regulatory submission process and have provided insights into optimal use of the drug. Sunitinib also illustrates some of the practical difficulties of evaluating exposure-response relationships in clinical trials in oncology. © 2011 American Association of Pharmaceutical Scientists.