2018 年第 12 期 第 13 卷

心血管药物戈米辛G对华法林药代动力学的影响

Effect of gomisin G on pharmacokinetics of warfarin

作者：郭欣君苏宏泉赵颖超贺文帅张广有刘娟张素英

英文作者：

单位：010010呼和浩特，内蒙古自治区人民医院心内科

英文单位：

关键词：戈米辛G；华法林；细胞色素P4502C9；基因多态性；药代动力学

英文关键词：

• 摘要：

• 【摘要】目的    观察心血管药物戈米辛G对华法林药代动力学的影响。方法    用高效液相色谱检测戈米辛G在体外对细胞色素P450 2C9（CYP2C9）*1、CYP2C9*2、CYP2C9*3酶的作用、半数抑制浓度和抑制时间依赖性，建立血浆样品华法林含量测定方法，检测SD大鼠体内戈米辛G对华法林药代动力学的影响。结果    戈米辛G对CYP2C9 3种基因型的抑制作用程度为CYP2C9*3>CYP2C9*2>CYP2C9*1。将华法林与戈米辛G联合作用于SD大鼠，结果表明，给药组与对照组比较，华法林的药时曲线下面积、最大血药浓度以及药物清除率与生物利用度比值差异无统计学意义［（172±26）μg/(ml·h)比（175±17）μg/(ml·h)、（69.8±0.8）mg/L比（83.9±1.1）mg/L、（0.13±0.05）mg/(kg·h)比（0.12±0.01）mg/(kg·h)］，而达峰时间以及半衰期则发生延长［（7.44±1.25）h比（1.98±0.08）h、（12.1±2.3）h比（8.4±2.2）h］，差异有统计学意义（P<0.05）。结论    戈米辛G对CYP2C9酶有抑制作用，且具有个体基因型差异；戈米辛G能够影响华法林的药代动力学过程，这可能与戈米辛G能够与华法林竞争CYP2C9酶的活性结合位点有关，从而抑制CYP2C9酶对华法林的代谢作用。

• 【Abstract】Objective    To observe the effect of gomisin G on pharmacokinetics of warfarin. Methods    Activities of cytochrome P450 2C9（CYP2C9）*1, CYP2C9*2 and CYP2C9*3 enzymes inhibited by gomisin G, the 50% inhibiting concentration, the time-dependent manner and warfarin content in plasma samples were detected by high efficiency liquid chromatography. The influence of gomisin G on warfarin pharmacokinetics in vivo of SD rats was analyzed. Results    Inhibition effects of gomisin G on the three genotypes were CYP2C9*3>CYP2C9*2>CYP2C9*1. After being treated by warfarin with or without pre-administration of gomisin G, area under curve, the maximum blood concentration and the clearance to bioavailability ratio of warfarin showed no significant changes in observation group compared to those in control group［（172±26）μg/(ml·h) vs （175±17）μg/(ml·h), （69.8±0.8）mg/L vs （83.9±1.1）mg/L, （0.13±0.05）mg/(kg·h) vs （0.12±0.01）mg/(kg·h)］（P>0.05）; the peak time and half life of warfarin significantly increased in observation group［（7.44±1.25）h vs （1.98±0.08）h,（12.1±2.3）h vs （8.4±2.2）h］（P<0.05）. Conclusions    Gomisin G has an inhibitory effect on CYP2C9 enzyme, which shows individual variants among different genotypes. Gomisin G can affect the pharmacokinetics of warfarin by competitively binding with the active site of CYP2C9 to inhibit warfarin metabolism.