本文選題：替格瑞洛　切入點：替格瑞洛活性代謝產(chǎn)物　出處：《中國醫(yī)院藥學(xué)雜志》2016年21期 　論文類型：期刊論文

【摘要】：目的:研究替格瑞洛在中國健康志愿者中藥動學(xué)及藥效學(xué),為其臨床合理使用提供依據(jù)。方法:選14名健康男性志愿者,分別單次口服替格瑞洛180 mg,在不同時間點采集血樣分別用于藥動力學(xué)及藥效學(xué)研究,其中藥動學(xué)采樣時間點為給藥前、給藥后0.5,1,1.5,2,3,4,5,6,8,12,16,24,36,48 h,藥效學(xué)采樣時間點為給藥前他和給藥后1,2,4,12,24,48 h,藥動學(xué)血漿樣品采用蛋白沉淀法處理,超高效液相色譜-串聯(lián)質(zhì)譜(UPLC-MS/MS)法測定原藥、活性代謝產(chǎn)物濃度;藥效學(xué)采用四通道血小板聚集儀測定ADP誘導(dǎo)的血小板聚集率,以血小板聚集抑制的變化程度作為替格瑞洛的藥效學(xué)指標(biāo)。用WinNonlin軟件處理所得數(shù)據(jù)。結(jié)果:14例健康受試者口服180 mg替格瑞洛后,替格瑞洛原藥、活性代謝產(chǎn)物AR-C124910XX在人體內(nèi)平均tmax分別為(1.9±0.6)h和(2.1±0.6)h,平均t1/2分別為(8.3±1.1)h和(9.7±2.5)h,平均Cmax分別為(1 447.0±532.2)ng·mL~(-1)和(384.5±90.2)ng·mL~(-1),平均AUC0-last為(9 023.0±3 285.4)ng·mL~(-1)·h和(3 445.0±723.2)ng·mL-1·h,平均AUC0-∞為(9 208.7±3 437.6)ng·mL~(-1)·h和(3 594.4±827.0)ng·mL~(-1)·h。替格瑞洛對血小板抑制的達(dá)峰時間為4h,對血小板抑制的最大效應(yīng)Emax為(75.9±11.9%)。替格瑞洛的抗血小板效應(yīng)隨替格瑞洛及AR-C124910XX降低而減弱。結(jié)論:本研究系統(tǒng)考察了14例健康志愿者服用替格瑞洛后的藥動學(xué)及藥效學(xué),為臨床使用替格瑞洛劑量調(diào)整、優(yōu)化治療方案提供了理論依據(jù)。
[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 鹵0.6hand 2.1 鹵0.6hrespectively, the average t1 / 2 was 8.3 鹵1.1hand the average Cmax was 9.7 鹵2.5h. the average Cmax was 1447.0 鹵532.2ng 路mL ~ (-1) and 384.5 鹵90.2ng 路mL ~ (-1), the average AUC0-last was 9 023.0 鹵3 285.4ng 路mL ~ (-1) 路h and 3445.0 鹵723.2ng 路mL-1 路h, the average AUC0- 鈭，

本文編號：1587201