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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 alpha 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 (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 (1/2)-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.
Lee et al. (Sun,) studied this question.