Pharmacokinetics of a ginseng saponin metabolite compound K in rats

Abstract

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), Vss (1677-2744 ml/kg), dose-normalized AUC (41.8-57.8 microg.min/ml based on 1 mg/kg) and t1/2. 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 microg.min/ml) compared with those at lower doses (4.50-10.5 microg.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.

Inhibition of P-Glycoprotein Leads to Improved Oral Bioavailability of Compound K, an Anticancer Metabolite of Red Ginseng Extract Produced by Gut Microflora

“…Considering the oral bioavailability of C-K is reported to be ϳ5% in rodents Paek et al, 2006), the current study demonstrated that the inhibition of P-gp should lead to significantly increased oral bioavailability of C-K. Our previous publication showed that the bioavailability of Rh2s, another active ginsenoside with a similar structure and also a solid substrate of P-gp, was increased from 1 to Ͼ30% by coadministering cyclosporine A in mice (Yang et al, 2011).…”

“…Despite the demonstration of the in vivo biotransformation of ginsenosides to C-K, C-K itself was reported to have low oral bioavailability (ϳ5%) in rats Paek et al, 2006). The absorption mechanism of C-K is generally considered to be passive diffusion, because one study showed that there was no difference between bidirectional transports in Caco-2 cells .…”

Bioconversion of Ginsenoside Rd into Compound K by Lactobacillus pentosus DC101 Isolated from Kimchi

“…1). Their structures were assessed using the proton and carbon nuclear magnetic resonance (NMR; 1 H-NMR, 13 C-NMR) spectrum method with a Fourier transform NMR spectrometer (Inova AS 400 MHz NMR system; Varian, Vernon Hills, IL, USA) and pyridine-d 5 …”

“…These ginsenosides were previously reported to exhibit various biological activities, including anti-inflammatory activity [1] and antitumor effects (inhibition of tumor-induced angiogenesis and prevention of tumor invasion and metastasis) [2,3], but these naturally occurring ginsenosides are poorly absorbed along human intestinal tracts [4]. Previous studies demonstrated that protopanaxadiol-type ginsenosides such as Rb1, Rb2, and Rc are metabolized by intestinal bacteria after oral administration of their final derivative, 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol, also called compound K. Compound K, reported to be easily absorbed by the human body, is the genuine active form of protopanaxadiol-type saponins [5], and it has recently attracted increasing interest because of its intriguing biological actions. Compound K was demonstrated to induce tumor cell apoptosis, inhibit tumor metastasis, and restrain tumor invasion [6][7][8][9][10].…”

Fabrication of Compound K-loaded Polymeric Micelle System and its Characterization in vitro and Oral Absorption Enhancement in vivo

“…Membrane inserts were moved to other wells containing the same volume of fresh medium every 15 minutes for 1 h. An aliquot (1 mL) of each sample was collected from the basolateral side and stored at −80 °C until LC/MS analysis. 4 The apparent permeability coefficients (P app ) were calculated according to the following Eq. (2): (2) where, P app is the apparent permeability coefficient in cm/s, dQ/dt is the permeability rate, A is the diffusion area of the monolayer (cm 2 ) and C 0 is the initial concentration of the CK.…”