Pharmacokinetics of a ginseng saponin metabolite compound K in rats

The absorption, dose‐linearity and pharmacokinetics of compound K, a major intestinal bacterial metabolite of ginsenosides, were evaluated in vitro and in vivo . Using the Caco‐2 cell monolayers, compound K showed moderate permeability with no directional effects, thus suggesting passive diffusion. After intravenous dose (i.v.; 1, 2, and 10 mg/kg), no significant dose‐dependency was found in Cl (17.3–31.3 ml/min/kg), V ss (1677–2744 ml/kg), dose‐normalized AUC (41.8–57.8 µg·min/ml based on 1 mg/kg) and t 1/2 . The extent of urinary excretion was minimal for both i.v. and oral doses. The extent of compound K recovered from the entire gastrointestinal tract at 24h were 24.4%–26.2% for i.v. doses and 54.3%–81.7% for oral doses. Following oral administration (doses 5–20 mg/kg), dose‐normalized AUC (based on 5 mg/kg) was increased at the 20 mg/kg dose (85.3 µg·min/ml) compared with those at lower doses (4.50–10.5 µg·min/ml). Subsequently, the absolute oral bioavailability ( F ) was increased from 1.8%–4.3% at the lower doses to 35.0% at the 20 mg/kg dose. The increased F could be related to the saturation of carrier‐mediated hepatic uptake and esterification of compound K with fatty acids in the liver. Copyright © 2005 John Wiley & Sons, Ltd.