Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents

Korean red ginseng (KRG, Panax ginseng C.A. Meyer) contains ginsenosides, which are metabolized into active metabolites with various pharmacological effects. This study assessed the in vivo exposure and accumulation of ginsenosides following single and repeated administration of KRG and its active ingredient, compound K, in experimental rodents. In Study 1, rats received KRG (2 g/kg) orally as a single dose or for 2, 4, and 8 wks. Repeated administration increased the maximum plasma concentrations (Cmax) of ginsenosides Rb1 and Rd compared to a single dose (Rb: 23.9 to 68.3 ng/mL; Rd: 8.5 to 30.8 ng/mL over 8 wks). Compound K was detected at 2.9 and 2.3 ng/mL of Cmax after 4 and 8 wks of continuous KRG administration, with no significant differences. In Study 2, oral administration of compound K (5 or 10 mg/kg) in rats resulted in accumulation factors of 4 and 7, respectively. Study 3 evaluated the oral bioavailability of compound K in mice (intravenous, 2 mg/kg; oral, 10 mg/kg), estimating it at approximately 12%. Additionally, network pharmacology and molecular docking simulation studies supported the clinical potential of compound K against inflammation-related diseases. These findings suggest that for substances like KRG, which undergo in vivo metabolic conversion after administration, repeated KRG administration alters pharmacokinetic profiles and should be taken into consideration in its application.