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), 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.
Paek
In Bok
IB
College of Pharmacy and Medicinal Resources Research Institute, Wonkwang University, Iksan 570-749, Republic of Korea.
Moon
Ya
Y
Kim
John
J
Ji
Hye Young
HY
Kim
Soon Ai
SA
Sohn
Dong Hwan
DH
Kim
Jae Baek
JB
Lee
Hye Suk
HS
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D036145:Ginsenosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007780:Lacticaseibacillus casei; D008297:Male; D005894:Panax / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D036145:Ginsenosides; C112772:ginsenoside compound K