Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Metabolism and Pharmacokinetics of Orally Administered Saikosaponin b1 in Conventional, Germ-Free and Eubacterium sp. A-44-Infected Gnotobiote Rats
Hiroaki KIDATeruaki AKAOMeselhy Ragab MESELHYMasao HATTORI
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1998 Volume 21 Issue 6 Pages 588-593

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Abstract

The metabolic fate of saikosaponin b1 (1) was investigated using conventional, germ-free and Eubacterium sp. A-44-infected gnotobiote rats. After the oral administration of 1 to germ-free rats at a dose of 50mg/kg, no metabolite was detected in the plasma, the cecal contents or the cumulative feces through the experiment. On the other hand, when 1 was orally given to the Eubacterium sp. A-44-infected gnotobiote rats, considerable amounts of its metabolites, prosaikogenin A (2) and saikogenin A (3), were detected in the rat plasma with the respective AUC0-10h values of 17 424 and 22 260pmol·min/ml, similar to the case of its oral administration to conventional rats (AUC0-10h values of 9 936 and 12 414pmol·min/ml for 2 and 3, respectively). Furthermore, significant amounts of both metabolites were detected in the cecal contents and the cumulative feces of the gnotobiote and conventional rats, but not in those of the germ-free rats, within 10h after the administration.Fecal and cecal activities of hydrolyzing 1 and 2 were found in the gnotobiote and conventional rats, though there were no detectable activities in the germ-free rats. Accordingly, both hydrolyzing activities in the intestinal bacteria, such as Eubacterium sp. A-44, are essential for the appearance of 2 and 3 in the rat plasma and cumulative feces, since orally administered 1 was poorly absorbed from the gastrointestinal tract.

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