title: Sunitinib in combination with clarithromycin or azithromycin - is there a risk of interaction or not?
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 C(max) for 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 AUC(0-t) of 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.
authors: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, Sw. Marii Magdaleny 14, PL 61-861 Poznań, Poland. szalekedyta@wp.pl
authors: Edyta
authors: E
authors: Szałek
authors: Agnieszka
authors: A
authors: Karbownik
authors: Wojciech
authors: W
authors: Połom
authors: Marcin
authors: M
authors: Matuszewski
authors: Katarzyna
authors: K
authors: Sobańska
authors: Hanna
authors: H
authors: Urjasz
authors: Tomasz
authors: T
authors: Grabowski
authors: Anna
authors: A
authors: Wolc
authors: Edmund
authors: E
authors: Grześkowiak
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D017963:Azithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D007211:Indoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007527:Isoenzymes; D008297:Male; D008657:Metabolic Clearance Rate; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D018570:Risk Assessment; D013056:Spectrophotometry, Ultraviolet; D000077210:Sunitinib
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D017963:Azithromycin; D051544:Cytochrome P-450 CYP3A; D017291:Clarithromycin; D000077210:Sunitinib