Pharmacokinetic characteristics and hepatic distribution of IH-901, a novel intestinal metabolite of ginseng saponin, in rats

We investigated the pharmacokinetic characteristics of 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH-901), a metabolite that is formed by intestinal bacteria, after its intravenous (i.v.) or oral administration in rats. We developed an LC/MS/MS-based method to analyze IH-901 levels in plasma, bile, urine and tissue homogenates and validated its use in a pharmacokinetic study. After i.v. administration of 3 - 30 mg/kg IH-901, it disappeared rapidly from the plasma at a phase followed by slow disappearance at beta phase (t(1/2,alpha) of 0.042 - 0.055 h and t(1/2,beta) of 6.98 - 10.6 h, respectively). The oral route slightly prolongs IH-901 plasma levels (terminal phase t(1/2) of 26.1 h) yet leads to a bioavailability of only 4.54%. Of the various organs tested, the liver contained the majority of the i.v. bolus or orally administered IH-901, and liver IH-901 levels shortly after i.v. administration were 6-fold higher than the initial plasma concentration. The R-h (hepatic recovery ratio) was calculated to be 0.417, and the uptake clearance (CLuptake) for i.v. administered IH-901 was 0.401 mL(.)min(-1.)g liver(-1). Additionally, IH-901 is mostly excreted into the bile, since 40.5% of the i.v.-administered dose (30 mg/kg) was recovered in the bile within 6 h, and only 15% was found in the urine. Moreover, at steady state after i.v. infusion of IH-901, C-ss,C-liver was about 11.3-fold higher than C-ss,C-plasma,C- whereas C-ss,C-bile was about (1)/(2)-fold lower than C-ss,C-liver. These results indicated that the liver is largely responsible for removing IH-901 from the circulation. Oral administration of IH-901 leads to a low bioavailability; thus, the parenteral route may be the suitable way to deliver IH-901 for clinical applications.