|
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 microg h/l
(90% confidence interval 119%-159%) and the C(max) from 287 +/- 67 to 623
+/- 192 microg/l (90% confidence interval 127%-152%). Similarly,
clarithromycin coadministration increased sildenafil AUC from 1407 +/- 380
to 3209 +/- 762 microg h/l (90% confidence interval 127%-161%) and C(max)
from 287 +/- 67 to 694 +/- 259 microg/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. |