Sunitinib in combination with clarithromycin or azithromycin – is there a risk of interaction or not?
Edyta Sza³ek
1, Agnieszka Karbownik
1, Wojciech Po³om
2, Marcin
Matuszewski
2, Katarzyna Sobañska
1, Hanna Urjasz
1, Tomasz Grabowski
3, Anna Wolc
4, Edmund Grzeœkowiak
11Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences,
w. Marii Magdaleny 14, PL 61-861 Poznañ, Poland
2Department of Urology, University Clinical Centre, Kliniczna 1a, PL 80-402 Gdañsk, Poland
3Polpharma Biologics, Trzy lipy 3, PL 80-172 Gdañsk, Poland
4Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Wo³yñska 33, PL 60-637 Poznañ, Poland
Correspondence: Edyta Sza³ek, e-mail: szalekedyta@wp.pl
Abstract:
Background: Macrolides are the most widely prescribed antibiotics. Clarithromycin is a well-known inhibitor of cytochrome P450 CYP3A4 and causes numerous drug interactions that are not found for azithromycin. CYP3A4 is involved in the metabolism of the new oral multikinase inhibitor sunitinib and its active N-desethyl metabolite (SU012662). This study investigated the effects of oral single dose of clarithromycin or azithromycin on the pharmacokinetics of sunitinib.
Methods: Rabbits were subjected to one of three study drug groups: sunitinib + clarithromycin (n = 6), sunitinib + azithromycin (n = 6), or sunitinib (n = 6). The rabbits were treated with sunitinib in the oral dose of 25 mg. Plasma concentrations of sunitinib were measured with validated HPLC method with UV detection.
Results: Comparison of the sunitinib Cmaxfor the sunitinib + clarithromycin group with that of the sunitinib group gave a ratio of 94.4% [90% confidence interval (CI) (76.1, 117.1)]; for the sunitinib + azithromycin group, the ratio was 106.2% (90% CI 85.5, 131.7). Comparison of the sunitinib AUC0-tof the sunitinib + clarithromycin and sunitinib + azithromycin groups with that of the sunitinib group showed ratios of 86.86% (90% CI 69.7, 108.3) and 99.8% (90% CI 80.1, 124.5), respectively.
Conclusions: No significant effect of the coadministration of clarithromycin or azithromycin on the pharmacokinetics of sunitinib in rabbits was found in this study.
Key words:
sunitinib, azithromycin, clarithromycin, interaction, pharmacokinetics, rabbits
1554 Pharmacological Reports, 2012, 64, 15541559 Pharmacological Reports 2012, 64, 15541559 ISSN 1734-1140
Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences