The effect of ciprofloxacin and clarithromycin on sildenafil oral bioavailability in human volunteers

• Published in: Biopharmaceutics & drug disposition 2006-03, Vol.27 (2), p.103-110
• Main Authors: Hedaya, Mohsen A., El-Afify, Dalia R., El-Maghraby, Gamal M.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - pharmacology; bioavailability; Biological and medical sciences; Biological Availability; Ciprofloxacin - administration & dosage; Ciprofloxacin - pharmacology; Clarithromycin - administration & dosage; Clarithromycin - pharmacology; CYP3A4 inhibitors; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - metabolism; Drug Interactions; Humans; Liver - drug effects; Liver - enzymology; Male; Medical sciences; pharmacokinetic interactions; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - administration & dosage; Phosphodiesterase Inhibitors - pharmacokinetics; Piperazines - administration & dosage; Piperazines - pharmacokinetics; Purines; sildenafil; Sildenafil Citrate; Sulfones
• ISSN: 0142-2782; 1099-081X
• DOI: 10.1002/bdd.488

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 1407 ± 380 to 2986 ± 917 µg h/l (90% confidence interval 119%–159%) and the Cmax from 287 ± 67 to 623 ± 192 µg/l (90% confidence interval 127%–152%). Similarly, clarithromycin coadministration increased sildenafil AUC from 1407 ± 380 to 3209 ± 762 µg h/l (90% confidence interval 127%–161%) and Cmax from 287 ± 67 to 694 ± 259 µg/l (90% confidence interval 132%–157%). Ciprofloxacin coadministration and clarithromycin coadministration with sildenafil did not affect the rate of sildenafil absorption significantly. These results indicate that coadministration of ciprofloxacin and clarithromycin significantly increased sildenafil bioavailability which can be attributed to the inhibitory effect of ciprofloxacin and clarithromycin on CYP3A4. Dose adjustment of sildenafil is thus necessary when administered with such drugs. Copyright © 2005 John Wiley & Sons, Ltd.