高脂高热量饮食对硫酸氢氯吡格雷片在中国健康人体内药动学的影响

目的:研究健康受试者空腹及高脂高热量饮食情况下口服硫酸氢氯吡格雷片的药动学特征。方法:60名男性健康志愿者单剂量、自身交叉口服硫酸氢氯吡格雷片75 mg。采用液相色谱-质谱联用(HPLC-MS/MS)法测定人血浆中氯吡格雷的浓度。用DAS3.2.3药动学软件计算药动学参数,并用SPSS17.0软件对主要参数进行统计分析。结果:空腹与进食后的主要药动学参数如下:C_max分别为(1 440±2 397)ng·L^-1和(4 155±2 117)ng·L^-1,AUC_0-36分别为(2 268±3 887)ng·L^-1·h和(8 691±3 628)ng·L^-1·h,AUC_0-∞分别为(2 324±3 899)ng·L^-1·h和(8 816±3 668)ng·L^-1·h,t_1/2分别为(5.7±4.7)h和(8.8±3.8)h,t_max分别为(0.7±0.5)h和(1.7±0.7)h, V_d分别为(520 115±471 187)L和(118 826±59 077)L,CL分别为(82 365±70 072)L·h^-1和(9 949±4 017)L·h^-1,MRT_0-36分别为(3.0±1.8)h和(3.6±0.9)h。结论:高脂高热量饮食对硫酸氢氯吡格雷片的药动学特征有显著影响,氯吡格雷的达峰时间延长,生物利用度提高,半衰期延长。

Effects of high fat and calory diet on pharmacokinetics of clopidogrel hydrogen sulfate tablets in Chinese healthy volunteers

OBJECTIVE To study effects of high fat and calory diet on pharmacokinetics of clopidogrel hydrogen sulfate tablets in Chinese healthy volunteers. METHODS A total of 60 healthy male volunteers were randomly assigned to receive single oral dose of clopidogrel hydrogen sulfate tablets 75 mg on empty stomach or in combination with high fat and calory diet following a randomized crossover design. Plasma concentrations of clopidogrel were measured by HPLC-MS/MS. Pharmacokinetic parameters were calculated by DAS3.2.3,and effects of high fat and calory diet on pharmacokinetics of clopidogrel were evaluated by SPSS 17.0. RESULTS Under fasted and fed conditions, main pharmacokinetic parameters of clopidogrel were as follows:C_max (1 440±2 397),(4 155±2 117) ng·L^-1,AUC_0-36 (2 268±3 887),(8 691±3 628) ng·L^-1·h, AUC_0-∞ (2 324±3 899), (8 816±3 668) ng·L^-1·h,t_1/2 (5.7±4.7),(8.8±3.8) h,t_max (0.7±0.5),(1.7±0.7) h,V_d (520 115±471 187),(11 8826±59 077) L,CL (82 365±70 072),(9 949±4 017) L·h^-1,MRT_0-36(3.0±1.8),(3.6±0.9) h. CONCLUSION High fat and calory diet has effects on pharmacokinetics of clopidogrel hydrogen sulfate tablets, with bioavailability as well as t_max and t_1/2 increased.