Individualized dosing of tyrosine kinase inhibitors: are we there yet?

Drug Discov Today. 2015 Jan;20(1):18-36. doi: 10.1016/j.drudis.2014.09.007. Epub 2014 Sep 22.


Tyrosine kinase inhibitors (TKIs) are registered at a fixed oral dose, despite their large variability in pharmacokinetics (PK). Given that the evidence for a relation between drug exposure and treatment outcome is growing, this one-dose-fits-all approach can unintentionally lead to under- and overexposure. Dose individualization could lower this variability and thereby beneficially effect treatment outcome. In this article, we explore whether TKIs used for solid tumors meet the criteria for dose individualization. Despite limitations such as retrospective analysis, current data suggest that the following Ctrough levels could be used: imatinib 1100ng/ml, sunitinib when continuously dosed 37.5ng/ml, intermittent 50ng/ml and pazopanib 20μg/ml. A comprehensive review of the literature also shows that prospective trials investigating the influence of dose individualization on treatment outcome are warranted.

Publication types

  • Review

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Precision Medicine
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / antagonists & inhibitors


  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases