Physiologically Based Pharmacokinetic Models of Tyrosine Kinase Inhibitors: A Systems Pharmacological Approach to Drug Disposition

The emergence of low‐molecular‐weight tyrosine kinase inhibitors (TKIs) has revolutionized anticancer drug therapy. It is not unexpected that lead TKIs are sought with favorable macropharmacokinetic characteristics, such as high oral bioavailability; however, surprisingly little emphasis has been given to the tissue disposition of TKIs, the site of drug action. This article discusses how physiologically based pharmacokinetic (PBPK) models can address this deficiency and help improve our understanding of the determinants of TKI efficacy. Clinical Pharmacology & Therapeutics (2013); 93 3, 236–238. doi:10.1038/clpt.2012.244