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.

中文翻译：

---

银杏萜内酯的人体药代动力学以及血液中羧化对其血小板活化因子拮抗活性的影响。

萜内酯是银杏叶提取物标准化制剂的一类生物活性成分，广泛用作缺血性心血管和脑血管疾病患者的附加疗法。这项研究评估了银杏萜内酯的人体药代动力学及其在血液中羧化的影响。人类受试者接受两种口服银杏通心片或静脉舒血宁，这是两种标准化的银杏制剂。在体外评估了它们的血浆蛋白结合和血小板活化因子拮抗活性。在磷酸缓冲盐溶液（pH 7.4）和人血浆中评估了它们的羧化作用。服用银杏通心片后，银杏内酯A和B以及银杏内酯的全身暴露水平明显高于银杏内酯C和J。服用舒雪宁后，银杏内酯A，B，C，和J表现出很高的暴露水平。化合物在血浆中的未结合分数为45-92％。银杏内酯A和B的表观口服生物利用度大多> 100％，而银杏内酯C和J的表观生物利用度为6-15％。Bilobalide的生物利用度可能较高，但低于Ginkgolides A / B。服用舒血宁后银杏内酯A，B和C的终末半衰期（4-7 h）短于服用银杏通心片后的终末半衰期（6-13 h）。给药片剂后，银杏内酯的半衰期为约5小时。萜内酯大致均匀地分布在各种体液和组织中。基于肾小球滤过的肾脏排泄是银杏内酯的主要消除途径，而银杏内酯的主要消除途径。萜内酯以三内酯和单羧酸酯形式循环。羧化作用会降低银杏内酯A，B和C的血小板活化因子拮抗活性。银杏内酯J，银杏内酯和银杏黄酮没有这种生物活性。总的来说，在研究萜内酯对银杏制剂的治疗效果的相对贡献时，应考虑两种制剂之间萜内酯的暴露差异以及它们在血液中羧化的影响。这里的结果将为银杏制剂的合理临床使用提供信息。在研究萜烯内酯对银杏制剂治疗效果的相对贡献时，应考虑两种制剂之间的接触以及它们在血液中羧化的影响。这里的结果将为银杏制剂的合理临床使用提供信息。在研究萜烯内酯对银杏制剂治疗效果的相对贡献时，应考虑两种制剂之间的接触以及它们在血液中羧化的影响。这里的结果将为银杏制剂的合理临床使用提供信息。