Abstract
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.
Highlights
Compound K, which belongs to the protopanaxadiol (PPD)-type ginsenoside group, was first discovered in 1972 from a hydrolase mixture of ginsenosides (Rb1, Rb2, and Rc) and soil bacteria [1]
The results suggested that the consumption of ginseng product with higher compound K content resulted in higher plasma concentrations of compound K
The pharmacokinetic parameters of compound K such as area under plasma concentration (AUC) and plasma concentration were about 5–6-fold greater in mice than in rats, while there was no significant difference in the half-life (T1/2) and mean residence time (MRT) between rats and mice (Table 3)
Summary
Compound K, which belongs to the protopanaxadiol (PPD)-type ginsenoside group, was first discovered in 1972 from a hydrolase mixture of ginsenosides (Rb1, Rb2, and Rc) and soil bacteria [1]. Paek et al [3] investigated the dose-dependent bioavailability of compound K by comparing its oral and intravenous administration in rats. The area under plasma concentration (AUC) of compound K increased linearly following intravenous injection at a dose range of 1–10 mg/kg (dose increase 10-fold; AUC increase 11.6-fold), but the AUC of compound K following oral administration did not increase linearly at a dose range of 5–20 mg/kg (dose increase four-fold; AUC increase 75.8-fold) [3]. The AUC of compound K was significantly increased (23.5-fold) in P-glycoprotein (P-gp) knock-out mice compared to wild-type mice after a single oral dose (10 mg/kg) [4]. P-gp-mediated efflux during intestinal absorption could be a possible explanation for non-linear oral bioavailability of compound K
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
