PT - JOURNAL ARTICLE AU - Houfu Liu AU - Junling Yang AU - Feifei Du AU - Xiumei Gao AU - Xutao Ma AU - Yuhong Huang AU - Fang Xu AU - Wei Niu AU - Fengqing Wang AU - Yu Mao AU - Yan Sun AU - Tong Lu AU - Changxiao Liu AU - Boli Zhang AU - Chuan Li TI - Absorption and Disposition of Ginsenosides after Oral Administration of <em>Panax notoginseng</em> Extract to Rats AID - 10.1124/dmd.109.029819 DP - 2009 Dec 01 TA - Drug Metabolism and Disposition PG - 2290--2298 VI - 37 IP - 12 4099 - http://dmd.aspetjournals.org/content/37/12/2290.short 4100 - http://dmd.aspetjournals.org/content/37/12/2290.full SO - Drug Metab Dispos2009 Dec 01; 37 AB - Panax notoginseng (Sanqi) is a cardiovascular herb containing ginsenosides that are believed to be responsible for the therapeutic effects of Sanqi. The aim of this study was to evaluate rat exposure to ginsenosides after oral administration of Sanqi extract and to identify the key factors affecting their absorption and disposition. Ginsenosides were administered to rats, either in the form of Sanqi extract or as pure chemicals. The ginsenosides Ra3, Rb1, Rd, Re, Rg1, and notoginsenoside R1 were the major saponins present in the herbal extract. Systemic exposure to ginsenosides Ra3, Rb1, and Rd after oral administration of the extract was significantly greater than that to the other compounds. Considerable colonic deglycosylation of the ginsenosides occurred, but the plasma levels of deglycosylated metabolites were low in rats. Poor membrane permeability and active biliary excretion are the two primary factors limiting systemic exposure to most ginsenosides and their deglycosylated metabolites. In contrast with other ginsenosides, biliary excretion of ginsenosides Ra3 and Rb1 was passive. Meanwhile, the active biliary excretion of ginsenoside Rd was significantly slower than that of other saponins. Slow biliary excretion, inefficient metabolism, and slow renal excretion resulted in long-circulating and thus relatively high exposure levels for these three ginsenosides. For these reasons, plasma ginsenosides Ra3, Rb1, and Rd were identified as pharmacokinetic markers for indicating rat systemic exposure to Sanqi extract. This is a systematic investigation of the absorption and disposition of ginsenosides from an herb, the information gained from which is important for linking Sanqi administration to its medicinal effects.Copyright © 2009 by The American Society for Pharmacology and Experimental Therapeutics