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Sunitinib in combination with clarithromycin or azithromycin - is there a risk of interaction or not?

Edyta Szałek1, Agnieszka Karbownik, Wojciech Połom

  • 1Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Sw. Marii Magdaleny 14, PL 61-861 Poznań, Poland. szalekedyta@wp.pl

Pharmacological Reports : PR
|February 15, 2013
PubMed
Abstract

Insights

Clarithromycin and azithromycin did not significantly alter sunitinib pharmacokinetics in rabbits. This study suggests no major drug interactions between these antibiotics and sunitinib, important for cancer patients.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Oncology

Background:

  • Macrolide antibiotics are widely prescribed.
  • Clarithromycin inhibits CYP3A4, unlike azithromycin, leading to drug interactions.
  • CYP3A4 metabolizes sunitinib, an oral multikinase inhibitor.

Purpose of the Study:

  • To investigate the impact of clarithromycin and azithromycin on sunitinib pharmacokinetics.
  • To assess potential drug-drug interactions between these macrolides and sunitinib.

Main Methods:

  • A study involving rabbits divided into three groups: sunitinib alone, sunitinib + clarithromycin, and sunitinib + azithromycin.
  • Sunitinib was administered orally at a dose of 25 mg.
  • Plasma concentrations of sunitinib were quantified using a validated High-Performance Liquid Chromatography (HPLC) method with UV detection.

Main Results:

  • Coadministration of clarithromycin resulted in a sunitinib Cmax ratio of 94.4% (90% CI 76.1, 117.1) and AUC(0-t) ratio of 86.86% (90% CI 69.7, 108.3).
  • Coadministration of azithromycin resulted in a sunitinib Cmax ratio of 106.2% (90% CI 85.5, 131.7) and AUC(0-t) ratio of 99.8% (90% CI 80.1, 124.5).
  • Confidence intervals for both Cmax and AUC(0-t) included 100%, indicating no statistically significant effect.

Conclusions:

  • Neither clarithromycin nor azithromycin significantly affected the pharmacokinetics of sunitinib in rabbits.
  • The findings suggest a lack of significant drug interaction between these macrolides and sunitinib in this animal model.
  • Further clinical studies may be warranted to confirm these findings in human patients.

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