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Intravenous formulation of Panax notoginseng root extract: human pharmacokinetics of ginsenosides and potential for perpetrating drug interactions

文献类型：期刊论文

作者Pintusophon, Salisa2,3; Niu, Wei3; Duan, Xiao-na2,3; Olaleye, Olajide E.3; Huang, Yu-hong1; Wang, Feng-qing3; Li, Yan-fen1; Yang, Jun-ling3; Li, Chuan2,3
刊名ACTA PHARMACOLOGICA SINICA
出版日期2019-10-01
卷号40期号:10页码:1351-1363
关键词ginsenoside cytochrome P450 3A organic anion-transporting polypeptide 1B3 herbal medicine-drug interactions XueShuanTong Panax notoginseng
ISSN号1671-4083
DOI10.1038/s41401-019-0273-1
通讯作者Yang, Jun-ling(yangjl@simm.ac.cn) ; Li, Chuan(chli@simm.ac.cn)
英文摘要XueShuanTong, a lyophilized extract of Panax notoginseng roots (Sanqi) for intravenous administration, is extensively used as add-on therapy in the treatment of ischemic heart and cerebrovascular diseases and comprises therapeutically active ginsenosides. Potential for XueShuanTong-drug interactions was determined; the investigation focused on cytochrome P450 (CYP)3A induction and organic anion-transporting polypeptide (OATP)1B inhibition. Ginsenosides considerably bioavailable for drug interactions were identified by dosing XueShuanTong in human subjects and their interaction-related pharmacokinetics were determined. The CYP3A induction potential was determined by repeatedly dosing XueShuanTong for 15 days in human subjects and by treating cryopreserved human hepatocytes with circulating ginsenosides; midazolam served as a probe substrate. Joint inhibition of OATP1B by XueShuanTong ginsenosides was assessed in vitro, and the data were processed using the Chou-Talalay method. Samples were analyzed by liquid chromatography/mass spectrometry. Ginsenosides Rb-1, Rd, and Rg(1) and notoginsenoside R-1 were the major circulating XueShuanTong compounds; their interaction-related pharmacokinetics comprised compound dose-dependent levels of systemic exposure and, for ginsenosides Rb-1 and Rd, long terminal half-lives (32-57 and 58-307 h, respectively) and low unbound fractions in plasma (0.8%-2.9% and 0.4%-3.0%, respectively). Dosing XueShuanTong did not induce CYP3A. Based on the pharmacokinetics and inhibitory potency of the ginsenosides, XueShuanTong was predicted to have high potential for OATP1B3-mediated drug interactions (attributed chiefly to ginsenoside Rb1) suggesting the need for further model-based determination of the interaction potential for XueShuanTong and, if necessary, a clinical drug interaction study. Increased awareness of ginsenosides' pharmacokinetics and XueShuanTong-drug interaction potential will help ensure the safe use of XueShuanTong and coadministered synthetic drugs.
WOS关键词ST-JOHNS-WORT ; ANION-TRANSPORTING POLYPEPTIDES ; GLYCOPROTEIN IN-VITRO ; HEPATIC-UPTAKE ; INHIBITION ; QUANTIFICATION ; METABOLITES ; ABSORPTION ; FELODIPINE ; INDUCTION
资助项目National Key R&D Program of China[2018YFC1704500] ; National Science and Technology Major Project of China Key New Drug Creation and Manufacturing Program[2012ZX09101201-005] ; National Science and Technology Major Project of China Key New Drug Creation and Manufacturing Program[2017ZX09301012-006] ; National Natural Science Foundation of China[81673582] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050306] ; National Basic Research Program of China[2012CB518403]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000488273100010
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/282666]  
专题新药研究国家重点实验室
通讯作者Yang, Jun-ling; Li, Chuan
作者单位1.Tianjin Univ Tradit Chinese Med, Affiliated Hosp 2, Tianjin 300250, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Pintusophon, Salisa,Niu, Wei,Duan, Xiao-na,et al. Intravenous formulation of Panax notoginseng root extract: human pharmacokinetics of ginsenosides and potential for perpetrating drug interactions[J]. ACTA PHARMACOLOGICA SINICA,2019,40(10):1351-1363.
APA Pintusophon, Salisa.,Niu, Wei.,Duan, Xiao-na.,Olaleye, Olajide E..,Huang, Yu-hong.,...&Li, Chuan.(2019).Intravenous formulation of Panax notoginseng root extract: human pharmacokinetics of ginsenosides and potential for perpetrating drug interactions.ACTA PHARMACOLOGICA SINICA,40(10),1351-1363.
MLA Pintusophon, Salisa,et al."Intravenous formulation of Panax notoginseng root extract: human pharmacokinetics of ginsenosides and potential for perpetrating drug interactions".ACTA PHARMACOLOGICA SINICA 40.10(2019):1351-1363.

入库方式： OAI收割

来源：上海药物研究所

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