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 micro g hr/L and the C max from 236 +/- 71 to 478 +/- 210 micro g/L. The CL tot/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 microg hr/L and C max from 236 +/- 71 to 520 +/- 176 microg/L. The CL tot/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