Pharmacokinetic Characteristics and Hepatic Distribution of IH-901, a Novel Intestinal Metabolite of Ginseng Saponin, in Rats

Abstract

We investigated the pharmacokinetic characteristics of 20-O-(β-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 α phase followed by slow disappearance at β phase (t_{1/2, α} of 0.042 - 0.055 h and t_{1/2, β} 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 (CL_uptake) 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,liver was about 11.3-fold higher than C_ss,plasma, whereas C_ss,bile was about œ-fold lower than C_ss,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.

Key words

Panax ginseng - Araliaceae - ginseng saponin metabolite (IH-901) - pharmacokinetics - hepatic distribution - bioavailability

References

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