title: Characterization of pharmacokinetic profiles and metabolic pathways of 20(S)-ginsenoside Rh1 in vivo and in vitro.
abstract: 20(S)-Ginsenoside Rh1 is one of the important protopanaxatriol ginsenosides and has been reported to be the main hydrolysis product reaching the systemic circulation after oral ingestion of ginseng. However, its pharmacokinetic characteristics and metabolic fate have never been reported. The present study was therefore designed to elucidate its pharmacokinetic profiles and metabolic pathways both in vivo and in vitro. The absolute bioavailability of 20(S)-ginsenoside Rh1 in rats was only 1.01 %. Identification of metabolites showed that, after intragastrical administration of ginsenoside Rh1, two mono-oxygenated metabolites were detected from the urine, bile, liver tissue, and intestinal tract content, while the de-glucosylated product, 20(S)-protopanaxatriol, was only found in the contents of the intestinal tract. An in vitro incubation study confirmed that the CYP450-catalyzed mono-oxygenation, the intestinal bacteria mediated de-glucosylation, and the gastric acid mediated hydration reaction were the main metabolic pathways of 20(S)-ginsenoside Rh1. The presystemic metabolism as evidenced from this study may partially explain its poor bioavailability.
authors.affiliation: Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Lai
authors.forename: Haiping
authors.initials: H
authors.lastname: Hao
authors.forename: Yitong
authors.initials: Y
authors.lastname: Liu
authors.forename: Chaonan
authors.initials: C
authors.lastname: Zheng
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.forename: Xijin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001682:Biological Availability; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D036145:Ginsenosides / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D036145:Ginsenosides; D010936:Plant Extracts; C425564:ginsenoside Rh1; D003577:Cytochrome P-450 Enzyme System