Pharmacokinetics of ginsenosides following repeated oral administration of red ginseng extract signifi cantly differ between species of experimental animals

We aimed to investigate ginsenoside pharmacokineticsin mice and rats following the repeated oraladministration of red ginseng extract (RGE) (2 g/kg/day for7 days). In mouse plasma, seven protopanaxadiol (PPD)-type ginsenosides (20(S)-ginsenoside Rb1, Rb2, Rc, Rd,Rg3, 20(S)-compound K, and 20(S)-PPD) and one protopanaxatriol(PPT)-type 20(S)-ginsenoside Re were detected,whereas 20(S)-ginsenoside Rb1, Rb2, Rc, Rd, 20(S)-PPD,and 20(S)-PPT were detected in rat plasma. The tetra- ortri-glycosylated PPD-type ginsenosides Rb1, Rb2, Rc, andRd, high content ginsenosides in RGE, showed high plasmaexposure, a short absorption time (Tmax), and a long eliminationtime (T1/2) among the ginsenosides detected in bothspecies. Among the deglycosylated metabolites existing inthe feces, 20(S)-compound K and 20(S)-PPD in mice and20(S)-PPD and 20(S)-PPT in rats were found in the plasmasamples. In addition to the differences in the ginsenosidesdetected in mice and rats, the Tmax and T1/2 of 20(S)-PPDand 20(S)-PPT in rats were greater than those in mice, suggestingthe species-dependent difference in the gut metabolismand absorption of ginsenosides in the pathway from20(S)-ginsenoside Rd to 20(S)-PPD and from 20(S)-ginsenosideRe to 20(S)-PPT. In conclusion, the choice of animalmodel should be the subject of careful consideration whenexploring the pharmacology of RGE with specific focus onthe plasma profile of an individual ginsenoside. KCI Citation Count: 18