Stereoselective pharmacokinetics of 25-methoxyl-dammarane-3β,12β,20-triol and its active demethyl-metabolite epimers in rats after oral and intravenous administration

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• 作者：Nan Shao^a ; Huan Jiang^a ; Xiaotong Wang^a ; Bo Yuan^a ; Yi Jin^a ; Mantong Song^b ; Yuqing Zhao^c ; Haiyan Xu^a ; ^{xhy1020@gmail.com} ; ^{xhy411@163.com}
• 关键词：25-OCH3-PPD ; 25-OH-PPD ; Stereospecific ; Pharmacokinetics ; Metabolism
• 刊名：Fitoterapia
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：116
• 期：Complete
• 页码：139-145
• 全文大小：495 K
• 卷排序：116

文摘

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 Cmax and 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.