Understanding Disease-Drug Interactions in Cancer Patients: Implications for Dosing Within the Therapeutic Window

Clin Pharmacol Ther. 2015 Jul;98(1):76-86. doi: 10.1002/cpt.128. Epub 2015 May 19.

Abstract

The human inflammatory response can result in the alteration of drug clearance through effects on metabolizing enzymes or transporters. In this article we briefly review the theory of how cancer can lead to indirect changes in drug metabolism, review acute phase proteins and cytokines as markers of changes in cytochrome P450 (CYP) activity in cancer patients, and provide clinical case examples of how the inflammation in advanced cancer patients can lead to altered CYP-mediated drug clearance.

Publication types

  • Review

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytokines / metabolism
  • Drug Interactions
  • Humans
  • Imidazoles / pharmacology
  • Indoles / pharmacokinetics
  • Inflammation / metabolism
  • Meta-Analysis as Topic
  • Midazolam / pharmacokinetics
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Protein Kinase C beta / antagonists & inhibitors
  • Pyridines / pharmacology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Acute-Phase Proteins
  • Cytokines
  • Imidazoles
  • Indoles
  • Pyridines
  • ralimetinib
  • Cytochrome P-450 Enzyme System
  • Protein Kinase C beta
  • p38 Mitogen-Activated Protein Kinases
  • Midazolam
  • enzastaurin