Abstract
The pharmacokinetics of L‐FMAUS after intravenous and oral administration (20, 50 and 100 mg/kg) to rats, gastrointestinal first‐pass effect of L‐FMAUS (50 mg/kg) in rats, in vitro stability of L‐FMAUS, blood partition of L‐FMAUS between plasma and blood cells of rat blood, and protein binding of L‐FMAUS to 4% human serum albumin were evaluated. L‐FMAUS is being evaluated in a preclinical study as a novel antiviral agent. Although the dose‐normalized AUC values of L‐FMAUS were not significantly different among the three doses after intravenous and oral administration, no trend was apparent between the dose and dose‐normalized AUC. After oral administration of L‐FMAUS (50 mg/kg), approximately 2.37% of the oral dose was not absorbed, and the extent of absolute oral bioavailability (F) was approximately 11.5%. The gastrointestinal first‐pass effect was approximately 85% of the oral dose. The first‐pass effects of L‐FMAUS in the lung, heart and liver were almost negligible, if any, in rats. Hence, the small F of L‐FMAUS in rats was mainly due to the considerable gastrointestinal first‐pass effect. L‐FMAUS was stable in rat gastric juices. The plasma‐to‐blood cells partition ratio of L‐FMAUS was 2.17 in rat blood. The plasma protein binding of L‐FMAUS in rats was 98.6%. Copyright © 2007 John Wiley & Sons, Ltd.