title: Stereoselective pharmacokinetics of 25-methoxyl-dammarane-3β,12β,20-triol and its active demethyl-metabolite epimers in rats after oral and intravenous administration.
abstract: Stereoselectivity of ginsenosides produced from the stereogenic carbon-20 has been proved to be closely related to drug action including pharmacodynamics and pharmacokinetics. 25-Methoxydammarane-3,12,20-triol (25-OCH3-PPD) and 25-hydoxyprotopanaxadiol (25-OH-PPD) are novel protopanaxadiol-type (PPD) sapogenins. 25-OH-PPD was also the in vivo bioactive demethyl-metabolite of 25-OCH3-PPD. The study aimed to investigate the influence of 20(R/S)-configuration on the pharmacokinetics of 20(R/S)-25-OCH3-PPD epimers and 20(R/S)-25-OH-PPD epimers. When rats were given 20(R/S)-25-OCH3-PPD epimers intravenously, the pharmacokinetic profiles of both epimers of 25-OCH3-PPD were similar, while the pharmacokinetic behaviors of their demethyl-metabolites were obviously different. After rats received an oral dose of 20(R/S)-25-OCH3-PPD epimers, the Cmaxand AUC values of 20(S)-25-OCH3-PPD were at least 100 times higher than those of 20(R)-25-OCH3-PPD. Stereoselective pharmacokinetics of 25-OH-PPD was observed in rats after i.v. and i.g. administration of 20(R/S)-25-OH-PPD epimers. In vitro metabolic kinetics results indicated that faster hepatic metabolism of R-epimer should be one of the crucial factors accounting for the stereospecific pharmacokinetics of 25-OCH3-PPD and 25-OH-PPD epimers.
authors.affiliation: Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Shao
authors.affiliation: Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: School of Public Health, Shenyang Medical Collage, Shenyang 110034, China.
authors.forename: Mantong
authors.initials: M
authors.lastname: Song
authors.affiliation: Traditional Chinese Material Medical School, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: xhy1020@gmail.com.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D036145:Ginsenosides / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014315:Triterpenes / Q000493:pharmacokinetics*; D000097669:Dammaranes
chemical_list: D036145:Ginsenosides; D014315:Triterpenes; C529607:25-hydroxyprotopanaxadiol; C517965:25-methoxydammarane-3,12,20-triol; D000097669:Dammaranes
keywords: 25-OCH(3)-PPD; 25-OH-PPD; Metabolism; Pharmacokinetics; Stereospecific