Pharmacokinetics and Intestinal Metabolism of Compound K in Rats and Mice

We aimed to investigate the plasma concentration, tissue distribution, and elimination of compound K following the intravenous administration of compound K (2 mg/kg) in rats and mice. The plasma concentrations of compound K in mice were much higher (about five-fold) than those in rats. In both rats and mice, compound K was mainly distributed in the liver and underwent biliary excretion. There was 28.4% fecal recovery of compound K in mice and 13.8% in rats, whereas its renal recovery was less than 0.1% in both rats and mice. Relative quantification of compound K and its metabolite protopanaxadiol (PPD) in rat bile and intestinal feces indicated that the metabolism from compound K into PPD occurred in the intestine but not in the plasma. Therefore, PPD detected in the plasma samples could have been absorbed from the intestine after metabolism in control rats, while PPD could not be detected in the plasma samples from bile duct cannulated rats. In conclusion, mice and rats shared common features such as exclusive liver distribution, major excretion pathway via biliary route, and intestinal metabolism to PPD. However, there were significant differences between rats and mice in the plasma concentrations of compound K and the fecal recovery of compound K and PPD.