Hedaya, M., El-Afify, D., El-Maghraby, G. (2005). THE EFFECT OF CIPROFLOXACIN AND CLARITHROMYCIN ON SILDENAFIL ORAL BIOAVAILABILITY IN HUMAN VOLUNTEERS. test, 28(1), 137-142. doi: 10.21608/bfsa.2005.65246
Mohsen A. Hedaya; Dalia R. El-Afify; Gamal M. El-Maghraby. "THE EFFECT OF CIPROFLOXACIN AND CLARITHROMYCIN ON SILDENAFIL ORAL BIOAVAILABILITY IN HUMAN VOLUNTEERS". test, 28, 1, 2005, 137-142. doi: 10.21608/bfsa.2005.65246
Hedaya, M., El-Afify, D., El-Maghraby, G. (2005). 'THE EFFECT OF CIPROFLOXACIN AND CLARITHROMYCIN ON SILDENAFIL ORAL BIOAVAILABILITY IN HUMAN VOLUNTEERS', test, 28(1), pp. 137-142. doi: 10.21608/bfsa.2005.65246
Hedaya, M., El-Afify, D., El-Maghraby, G. THE EFFECT OF CIPROFLOXACIN AND CLARITHROMYCIN ON SILDENAFIL ORAL BIOAVAILABILITY IN HUMAN VOLUNTEERS. test, 2005; 28(1): 137-142. doi: 10.21608/bfsa.2005.65246

THE EFFECT OF CIPROFLOXACIN AND CLARITHROMYCIN ON SILDENAFIL ORAL BIOAVAILABILITY IN HUMAN VOLUNTEERS

Bulletin of Pharmaceutical Sciences Assiut University
Article 15, Volume 28, Issue 1, June 2005, Pages 137-142    PDF (281.02 K)
Document Type: Original Article
DOI: 10.21608/bfsa.2005.65246
Authors
Mohsen A. Hedaya1; Dalia R. El-Afify1; Gamal M. El-Maghraby2
1Department of Clinical Pharmacy
2Department of Pharmaceutical Technology, College of Pharmacy, University of Tanta, Tanta – Egypt
Abstract
Sildenafil is the first oral therapeutic agent for the management of male erectile dysfunction. Its oral bioavailability is only 40% due to extensive presystemic elimination, mainly by CYP3A4. This study examined the effect of coadministration of ciprofloxacin or clarithromycin which inhibit CYP3A4 on the bioavailability and pharmacokinetics of sildenafil. Twelve healthy male volunteers received sildenafil alone or after pretreatment with the inhibitors in a balanced three-way crossover design. The pharmacokinetic analysis showed that ciprofloxacin coadministration with sildenafil significantly increased the AUC from 1336±407 to 2751±968 µg hr/L and the Cmax from 236±71 to 478±210 µg/L. The CLtot/F was decreased from 40.1±9.9 to 20.9±8.6 L/hr and the Vd/F from 134.9±9.9 to 89.1±31.8 L, without affecting sildenafil elimination and absorption rate constants. Similarly, clarithromycin coadministration increased sildenafil AUC from 1336±407 to 2920±666 µg hr/L and Cmax from 236±71 to 520±176 µg/L. The CLtot/F significantly decreased from 40.1±9.9 to 18.1±5.0 L/hr and the Vd/F from 134.9±9.9 to 71.6±27.4 L, without affecting sildenafil elimination and absorption rate constants. These results indicate that coadministration of ciprofloxacin and clarithromycin significantly increased sildenafil bioavailability which can be inhibitory effect of ciprofloxacin and clarithromycin on CYP3A4. Dose adjustment of sidenafil is thus necessary when administered with such drugs.
Statistics
Article View: 105
PDF Download: 801