Pharmacokinetics, Modeling, and Simulation in the Development of Sunitinib Malate: A Case Study



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.


Renal Cell Carcinoma Acute Myeloid Leukemia Absolute Neutrophil Count Interindividual Variability Population Pharmacokinetic Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The content of two portions of this chapter has been adapted from two publications: Houk et al. (2009) was reproduced and adapted with permission from the American Association for Cancer Research and Houk et al. (2010) was adapted with kind permission of Springer Science and Business Media. Medical writing support was provided by Wendy Sacks at ACUMED (Tytherington, UK) and was funded by Pfizer Inc.


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Oncology Clinical PharmacologyLa JollaUSA

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