Greenblatt David J, von Moltke Lisa L, Luo Yan, Perloff Elke S, Horan Kelly A, Bruce Allison, Reynolds Robyn C, Harmatz Jerold S, Avula Bharathi, Khan Ikhlas A, Goldman Peter
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
J Clin Pharmacol. 2006 Feb;46(2):214-21. doi: 10.1177/0091270005283465.
The effect of Ginkgo biloba on the activity of CYP2C9, the isoform responsible for S-warfarin clearance, was assessed in 11 healthy volunteers who received single 100-mg doses of flurbiprofen, a probe substrate for CYP2C9. Subjects also received either a standardized G biloba leaf preparation (Ginkgold, 3 doses of 120 mg) or matching placebo in a randomized, double-blind, 2-way crossover study. Mean kinetic variables for flurbiprofen with either placebo or G biloba were elimination half-life, 3.9 versus 3.5 hours; total AUC, 57 versus 55 microg/mL h; and oral clearance, 32.9 versus 31.6 mL/min. None of these differences was significant. Based on highperformance liquid chromatography analysis, each 60-mg Ginkgold tablet contained 6.6 mug of amentoflavone and 61.2 microg of quercetin, both previously identified as CYP2C9 inhibitors. These amounts were apparently too low to inhibit CYP2C9 function in vivo. The results confirm previous controlled clinical studies showing no effect of ginkgo on the kinetics or dynamics of warfarin.
在11名健康志愿者中评估了银杏叶对CYP2C9活性的影响,CYP2C9是负责S-华法林清除的同工酶,这些志愿者接受了单剂量100 mg的氟比洛芬,这是一种CYP2C9的探针底物。在一项随机、双盲、双向交叉研究中,受试者还接受了标准化的银杏叶制剂(金纳多,3剂,每剂120 mg)或匹配的安慰剂。服用安慰剂或银杏叶后,氟比洛芬的平均动力学变量为:消除半衰期,分别为3.9小时和3.5小时;总AUC,分别为57和55μg/mL·h;口服清除率,分别为32.9和31.6 mL/min。这些差异均无统计学意义。基于高效液相色谱分析,每片60 mg的金纳多片剂含有6.6μg的穗花杉双黄酮和61.2μg的槲皮素,这两种物质先前均被鉴定为CYP2C9抑制剂。这些含量显然过低,无法在体内抑制CYP2C9的功能。结果证实了先前的对照临床研究,即银杏叶对华法林的动力学或药效学没有影响。