Guiding precision medicine strategy for intravenous ginsenosides via pharmacokinetic-informed bioinformatic approaches: a study on XueShuanTong
文献类型：期刊论文
| 作者 | Jia, Wei-Wei3,4; Tian, Nan-Nan3,4; Song, Zi-Jing2; Lan, Xiao-Fang4; Yang, Xi-He4; Du, Fei-Fei4; Wang, Feng-Qing4; Cheng, Chen4; Xia, Xiao-Yan1; Zeng, Yi-Mei2 |
| 刊名 | PHYTOMEDICINE
 |
| 出版日期 | 2025-07-25 |
| 卷号 | 143页码:18 |
| 关键词 | Precision medicine Physiologically based pharmacokinetic model Ginsenoside Albumin-facilitated dissociation Drug interaction Drug transporter Hepatic impairment |
| ISSN号 | 0944-7113 |
| DOI | 10.1016/j.phymed.2025.156716 |
| 英文摘要 | Background: Intravenous ginsenosides, derived from Panax species, are widely used in China. XueShuanTong injection, enriched with ginsenosides Rb1 and Rg1, is recommended for unstable angina treatment. Although effective, it may cause adverse effects, especially in patients with renal or hepatic impairment, as these organs are vital in ginsenosides' systemic exposure. Purpose: This investigation aimed to inform precision medicine by employing a physiologically based pharmacokinetic (PBPK) model to evaluate transporter-mediated interactions between both ginsenosides and their systemic exposure in patients with organ impairment, thereby ensuring safety. Methods: Interactions between ginsenosides Rb1 and Rg1, mediated by human and rat transporters, were characterized at both cellular and vesicular levels. Their interactions with human organic anion-transporting poly-peptide (OATP)1B3 and rat Oatp1b2 were evaluated when administered together or as part of XueShuanTong in both rats and humans. PBPK models incorporating OATP-mediated hepatobiliary excretion were developed to characterize their interactions and pharmacokinetics, providing guidance for precision medicine in these patients. Results: Ginsenoside Rb1 was demonstrated to inhibit human OATP1B3 (Oatp1b2 in rats)-mediated cellular uptake, significantly increasing exposure levels of ginsenoside Rg1 in rats by impairing hepatobiliary elimination. Mechanistic models effectively replicated the pharmacokinetic profiles and the interactions of ginsenosides Rb1 and Rg1. These validated models revealed that decreases in GFR, hematocrit, hepatic volume, and/or OATP1B3 expression and activity in patients with renal or hepatic impairment significantly increased the systemic exposure levels of both ginsenosides. Moreover, the models provided valuable insights into the mechanism of "albumin-facilitated dissociation" associated with ginsenoside Rb1, an OATP1B3 inhibitor. This understanding is crucial for predicting the risk of drug-drug interactions involving drugs with high plasma protein binding. |
| WOS关键词 | MOLECULAR-MECHANISMS |
| 资助项目 | National Natural Science Foundation of China[82274351] ; National Natural Science Foundation of China[82192912] ; National Natural Science Foundation of China[81603380] ; National Science and Technology Major Project of China Key New Drug Creation and Manufacturing Program[2012ZX09101201-005] ; National Key R & D Program Strategic Scientific and Technological Innovation Cooperation Key Project[2022YFE0203600] |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001508689000001 |
| 出版者 | ELSEVIER GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318413]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Jia, Wei-Wei; Yang, Jun-Ling; Li, Chuan |
| 作者单位 | 1.Chinese Acad Sci, Univ Chinese Acad Sci, Sch Pharm, Shanghai 201203, Peoples R China 2.Zhongshan Inst Drug Discovery, Zhongshan 528400, Peoples R China 3.Tianjin Univ Tradit Chinese Med, Tianjin 300193, Peoples R China 4.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 | Jia, Wei-Wei,Tian, Nan-Nan,Song, Zi-Jing,et al. Guiding precision medicine strategy for intravenous ginsenosides via pharmacokinetic-informed bioinformatic approaches: a study on XueShuanTong[J]. PHYTOMEDICINE,2025,143:18. |
| APA | Jia, Wei-Wei.,Tian, Nan-Nan.,Song, Zi-Jing.,Lan, Xiao-Fang.,Yang, Xi-He.,...&Li, Chuan.(2025).Guiding precision medicine strategy for intravenous ginsenosides via pharmacokinetic-informed bioinformatic approaches: a study on XueShuanTong.PHYTOMEDICINE,143,18. |
| MLA | Jia, Wei-Wei,et al."Guiding precision medicine strategy for intravenous ginsenosides via pharmacokinetic-informed bioinformatic approaches: a study on XueShuanTong".PHYTOMEDICINE 143(2025):18. |
入库方式： OAI收割
来源：上海药物研究所
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