银杏和生姜对健康受试者华法林药代动力学和药效学的影响。
Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.
作者信息
Jiang Xuemin, Williams Kenneth M, Liauw Winston S, Ammit Alaina J, Roufogalis Basil D, Duke Colin C, Day Richard O, McLachlan Andrew J
机构信息
Faculty of Pharmacy, The University of Sydney, NSW, Australia.
出版信息
Br J Clin Pharmacol. 2005 Apr;59(4):425-32. doi: 10.1111/j.1365-2125.2005.02322.x.
AIM
The aim of this study was to investigate the effect of two common herbal medicines, ginkgo and ginger, on the pharmacokinetics and pharmacodynamics of warfarin and the independent effect of these herbs on clotting status.
METHODS
This was an open label, three-way crossover randomized study in 12 healthy male subjects, who received a single 25 mg dose of warfarin alone or after 7 days pretreatment with recommended doses of ginkgo or ginger from herbal medicine products of known quality. Dosing with ginkgo or ginger was continued for 7 days after administration of the warfarin dose. Platelet aggregation, international normalized ratio (INR) of prothrombin time, warfarin enantiomer protein binding, warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured. Statistical comparisons were made using anova and the 90% confidence intervals (CIs) of the ratio of log transformed parameters are reported.
RESULTS
INR and platelet aggregation were not affected by administration of ginkgo or ginger alone. The mean (95% CI) apparent clearances of S-warfarin after warfarin alone, with ginkgo or ginger were 189 (167-210) ml h(-1), 200 (173-227) ml h(-1) and 201 (171-231) ml h(-1), respectively. The respective apparent clearances of R-warfarin were 127 (106-149) ml h(-1), 126 (111-141) ml h(-1) and 131 (106-156) ml h(-1). The mean ratio (90% CI) of apparent clearance for S-warfarin was 1.05 (0.98-1.21) and for R-warfarin was 1.00 (0.93-1.08) when coadministered with ginkgo. The mean ratio (90% CI) of AUC(0-168) of INR was 0.93 (0.81-1.05) when coadministered with ginkgo. The mean ratio (90% CI) of apparent clearance for S-warfarin was 1.05 (0.97-1.13) and for R-warfarin was 1.02 (0.95-1.10) when coadministered with ginger. The mean ratio (90% CI) of AUC(0-168) of INR was 1.01 (0.93-1.15) when coadministered with ginger. The mean ratio (90% CI) for S-7-hydroxywarfarin urinary excretion rate was 1.07 (0.85-1.32) for ginkgo treatment, and 1.00 (0.81-1.23) for ginger coadministration suggesting these herbs did not affect CYP2C9 activity. Ginkgo and ginger did not affect the apparent volumes of distribution or protein binding of either S-warfarin or R-warfarin.
CONCLUSIONS
Ginkgo and ginger at recommended doses do not significantly affect clotting status, the pharmacokinetics or pharmacodynamics of warfarin in healthy subjects.
目的
本研究旨在探讨两种常见草药银杏和生姜对华法林药代动力学和药效学的影响，以及这些草药对凝血状态的独立作用。
方法
这是一项开放标签、三交叉随机研究，纳入12名健康男性受试者，他们单独接受一次25mg剂量的华法林，或在使用已知质量的草药产品中推荐剂量的银杏或生姜预处理7天后再接受华法林。在给予华法林剂量后，继续使用银杏或生姜给药7天。测量血小板聚集、凝血酶原时间的国际标准化比值（INR）、华法林对映体蛋白结合、血浆中华法林对映体浓度以及尿中S-7-羟基华法林浓度。使用方差分析进行统计比较，并报告对数转换参数比值的90%置信区间（CIs）。
结果
单独给予银杏或生姜不影响INR和血小板聚集。单独使用华法林、与银杏或生姜合用时，S-华法林的平均（95%CI）表观清除率分别为189（167 - 210）ml h⁻¹、200（173 - 227）ml h⁻¹和201（171 - 231）ml h⁻¹。R-华法林的相应表观清除率分别为127（106 - 149）ml h⁻¹、126（111 - 141）ml h⁻¹和131（106 - 156）ml h⁻¹。与银杏合用时，S-华法林表观清除率的平均比值（90%CI）为1.05（0.98 - 1.21），R-华法林为1.00（0.93 - 1.08）。与银杏合用时，INR的AUC(0 - 168)平均比值（90%CI）为0.93（0.81 - 1.05）。与生姜合用时，S-华法林表观清除率的平均比值（90%CI）为1.05（0.97 - 1.13）,R-华法林为1.02（0.95 - 1.10）。与生姜合用时，INR的AUC(0 - 168)平均比值（90%CI）为1.01（0.93 - 1.15）。银杏治疗时，S-7-羟基华法林尿排泄率的平均比值（90%CI）为1.07（0.85 - 1.32），生姜合用为1.00（0.81 - 1.23），提示这些草药不影响CYP2C9活性。银杏和生姜不影响S-华法林或R-华法林的表观分布容积或蛋白结合。
结论
推荐剂量的银杏和生姜对健康受试者的凝血状态、华法林的药代动力学和药效学无显著影响。
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