humanpharmacokineticsofginkgoterpenelactonesandimpactofcarboxylationinbloodontheirplateletactivatingfactorantagonisticactivity
文献类型：期刊论文
| 作者 | Liu Xinwei1; Yang Junling1 ; Niu Wei1; Jia Weiwei1; Olaleye Olajide E1; Wen Qi1; Duan Xiaona1; Huang Yuhong2; Wang Fengqing1; Du Feifei1
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| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2018 |
| 卷号 | 39期号:12页码:1935 |
| 关键词 | FACTOR PAF-ACETHER ENDOTHELIAL-CELLS BILOBA EXTRACTS INHIBITION METABOLISM QUERCETIN PLASMA RUTIN PON1 PARAOXONASES Ginkgo biloba human pharmacokinetics renal excretion terpene lactone monocarboxylate platelet-activating factor |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-018-0086-7 |
| 英文摘要 | Terpene lactones are a class of bioactive constituents of standardized preparations of Ginkgo biloba leaf extract, extensively used as add-on therapies in patients with ischemic cardiovascular and cerebrovascular diseases. This investigation evaluated human pharmacokinetics of ginkgo terpene lactones and impact of their carboxylation in blood. Human subjects received oral YinXing- TongZhi tablet or intravenous ShuXueNing, two standardized ginkgo preparations. Their plasma protein-binding and platelet-activating factor antagonistic activity were assessed in vitro. Their carboxylation was assessed in phosphate-buffered saline (pH 7.4) and in human plasma. After dosing YinXing-TongZhi tablet, ginkgolides A and B and bilobalide exhibited significantly higher systemic exposure levels than ginkgolides C and J; after dosing ShuXueNing, ginkgolides A, B, C, and J exhibited high exposure levels. The compounds' unbound fractions in plasma were 45-92%. Apparent oral bioavailability of ginkgolides A and B was mostly >100%, while that of ginkgolides C and J was 6-15%. Bilobalide's bioavailability was probably high but lower than that of ginkgolides A/B. Terminal half-lives of ginkgolides A, B, and C (4-7 h) after dosing ShuXueNing were shorter than their respective values (6-13 h) after dosing YinXing-TongZhi tablet. Half-life of bilobalide after dosing the tablet was around 5 h. Terpene lactones were roughly evenly distributed in various body fluids and tissues; glomerular-filtration-based renal excretion was the predominant elimination route for the ginkgolides and a major route for bilobalide. Terpene lactones circulated as trilactones and monocarboxylates. Carboxylation reduced platelet-activating factor antagonistic activity of ginkgolides A, B, and C. Ginkgolide J, bilobalide, and ginkgo flavonoids exhibited no such bioactivity. Collectively, differences in terpene lactones' exposure between the two preparations and influence of their carboxylation in blood should be considered in investigating the relative contributions of terpene lactones to ginkgo preparations' therapeutic effects. The results here will inform rational clinical use of ginkgo preparations. |
| 资助项目 | [Science & Technology Commission of Shanghai Municipality] ; [National Science & Technology Major Project of China "Key New Drug Creation and Manufacturing Program"] ; [National Science Foundation of China for Distinguished Young Scholars] ; [Strategic Priority Research Program of the Chinese Academy of Sciences] |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/284516]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国科学院上海药物研究所 2.天津中医药大学 3.SPH XingLing Science & Technology Pharmaceutical Co., Ltd. |
| 推荐引用方式 GB/T 7714 | Liu Xinwei,Yang Junling,Niu Wei,et al. humanpharmacokineticsofginkgoterpenelactonesandimpactofcarboxylationinbloodontheirplateletactivatingfactorantagonisticactivity[J]. actapharmacologicasinica,2018,39(12):1935. |
| APA | Liu Xinwei.,Yang Junling.,Niu Wei.,Jia Weiwei.,Olaleye Olajide E.,...&Li Chuan.(2018).humanpharmacokineticsofginkgoterpenelactonesandimpactofcarboxylationinbloodontheirplateletactivatingfactorantagonisticactivity.actapharmacologicasinica,39(12),1935. |
| MLA | Liu Xinwei,et al."humanpharmacokineticsofginkgoterpenelactonesandimpactofcarboxylationinbloodontheirplateletactivatingfactorantagonisticactivity".actapharmacologicasinica 39.12(2018):1935. |
入库方式： OAI收割
来源：上海药物研究所
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