Pharmacokinetics and tissue distribution of 25-hydroxyprotopanaxadiol, an anti-cancer compound isolated from Panax ginseng, in athymic mice bearing xenografts of human pancreatic tumors

To determine pharmacokinetics and tissue distribution of 25-hydroxyprotopanaxadiol [25-OH-PPD, 20(R)-dammarane-3 beta,12 beta,20,25-tetrol], a promising antitumor natural product isolated from the fruits of Panax ginseng, an analytical method involving liquid chromatography/tandem mass spectrometry in biological samples was developed and employed. After intravenous and oral administration to nude mice bearing xenografts of human pancreatic tumors at doses of 10 and 20 mg/kg body weight, respectively, 25-OH-PPD was rapidly absorbed and distributed in plasma and in all tissues examined, including the tumors, with all C-max > 2 mu g/ml or mu g/g and t(max) < 1 h. The absolute oral bioavailability of 25-OH-PPD was relatively high, compared with other ginsenosides. These results indicate that this novel anti-cancer ginsenoside has relatively favorable pharmacokinetic properties and provide a basis for further development of this compound as a chemotherapeutic agent.