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Metabolism considerations for kinase inhibitors in cancer treatment

Derek R Duckett1, Michael D Cameron

  • 1Scripps Florida, The Scripps Research Institute, Department of Molecular Therapeutics, 130 Scripps Way, Jupiter, FL 33458, USA.

Expert Opinion on Drug Metabolism & Toxicology
|August 6, 2010
PubMed
Abstract

Insights

Protein kinase inhibitors are vital cancer therapies. This review covers eight approved small molecule kinase inhibitors, detailing their biology, metabolism, and drug interactions, highlighting transporter influence and reactive metabolite formation.

Area of Science:

  • Oncology
  • Pharmacology
  • Drug Development

Background:

  • Protein kinase inhibitors represent a significant advancement in targeted cancer therapy.
  • Pharmaceutical industry efforts have yielded successful clinical development of these targeted agents.

Purpose of the Study:

  • To review eight approved small molecule kinase inhibitors for cancer treatment.
  • To discuss inhibitor biology, selectivity, toxicity, metabolism, and drug interactions.

Main Methods:

  • Review of eight approved kinase inhibitors (imatinib, sorafenib, gefitinib, erlotinib, dasatinib, lapatinib, sunitinib, nilotinib).
  • Analysis of inhibitor selectivity, toxicity, metabolism, drug transporters, and drug-drug interactions.

Main Results:

  • Detailed discussion on the biology, selectivity, and toxicity of each inhibitor.
  • In-depth analysis of metabolism, drug transporters, and drug-drug interactions for each compound.
  • Identification of reactive metabolite formation for gefitinib, erlotinib, and dasatinib.

Conclusions:

  • Drug transporters and CYP3A4 interactions significantly influence approved kinase inhibitors.
  • Reactive metabolites are formed by gefitinib, erlotinib, and dasatinib, with implications for toxicity.

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