替格瑞洛在中国健康男性志愿者中的药动学及药效学研究

发布时间：2018-03-09 05:28

  本文选题：替格瑞洛　切入点：替格瑞洛活性代谢产物　出处：《中国医院药学杂志》2016年21期 　论文类型：期刊论文

【摘要】：目的:研究替格瑞洛在中国健康志愿者中药动学及药效学,为其临床合理使用提供依据。方法:选14名健康男性志愿者,分别单次口服替格瑞洛180 mg,在不同时间点采集血样分别用于药动力学及药效学研究,其中药动学采样时间点为给药前、给药后0.5,1,1.5,2,3,4,5,6,8,12,16,24,36,48 h,药效学采样时间点为给药前他和给药后1,2,4,12,24,48 h,药动学血浆样品采用蛋白沉淀法处理,超高效液相色谱-串联质谱(UPLC-MS/MS)法测定原药、活性代谢产物浓度;药效学采用四通道血小板聚集仪测定ADP诱导的血小板聚集率,以血小板聚集抑制的变化程度作为替格瑞洛的药效学指标。用WinNonlin软件处理所得数据。结果:14例健康受试者口服180 mg替格瑞洛后,替格瑞洛原药、活性代谢产物AR-C124910XX在人体内平均tmax分别为(1.9±0.6)h和(2.1±0.6)h,平均t1/2分别为(8.3±1.1)h和(9.7±2.5)h,平均Cmax分别为(1 447.0±532.2)ng·mL~(-1)和(384.5±90.2)ng·mL~(-1),平均AUC0-last为(9 023.0±3 285.4)ng·mL~(-1)·h和(3 445.0±723.2)ng·mL-1·h,平均AUC0-∞为(9 208.7±3 437.6)ng·mL~(-1)·h和(3 594.4±827.0)ng·mL~(-1)·h。替格瑞洛对血小板抑制的达峰时间为4h,对血小板抑制的最大效应Emax为(75.9±11.9%)。替格瑞洛的抗血小板效应随替格瑞洛及AR-C124910XX降低而减弱。结论:本研究系统考察了14例健康志愿者服用替格瑞洛后的药动学及药效学,为临床使用替格瑞洛剂量调整、优化治疗方案提供了理论依据。
[Abstract]:Objective: to study the pharmacokinetics and pharmacodynamics of tigrilol in Chinese healthy volunteers, and to provide evidence for its rational clinical use. Methods: fourteen healthy male volunteers were selected. Blood samples were collected at different time points for pharmacokinetics and pharmacodynamics study. The pharmacokinetic sampling time point of Chinese medicine was before administration. The pharmacodynamic sampling time was: before and after administration, the pharmacokinetic plasma samples were treated with protein precipitation method and the concentration of active metabolites was determined by UPLC-MS / MS method, and the pharmacokinetic plasma samples were treated by protein precipitation method, and the concentration of active metabolites was determined by UPLC-MS / MS method. The pharmacodynamics of the drug was determined by UPLC-MS / MSM method, and the pharmacodynamic sampling time was as follows: before and after administration, the pharmacokinetic plasma samples were treated by protein precipitation method and the concentration of active metabolites was determined by UPLC-MS / MS method. The pharmacodynamics of ADP induced platelet aggregation was measured by a four-channel platelet aggregator. The change of platelet aggregation inhibition was used as the pharmacodynamic index of tigrilol. The data were processed with WinNonlin software. The average tmax of active metabolite AR-C124910XX in human body were 1.9 卤0.6hand 2.1 卤0.6hrespectively, the average t1 / 2 was 8.3 卤1.1hand the average Cmax was 9.7 卤2.5h. the average Cmax was 1447.0 卤532.2ng 路mL ~ (-1) and 384.5 卤90.2ng 路mL ~ (-1), the average AUC0-last was 9 023.0 卤3 285.4ng 路mL ~ (-1) 路h and 3445.0 卤723.2ng 路mL-1 路h, the average AUC0- 鈭，

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