【摘要】 目的:研究液相色谱-质谱法测定人血浆中的复方赖诺普利,并分析高蛋白高脂肪食物对其药动学的影响。方法:采用随机双周期交叉设计,12名健康受试者(男女各半)随机分为2组,Ⅰ组空腹服复方赖诺普利片1片(每片含赖诺普利10．0 mg,氢氯噻嗪12．5 mg),Ⅱ组进食后服复方赖诺普利片1片,交叉间隔为1 wk。结果:空腹和进食单剂量口服受试制剂:赖诺普利的tmax分别为(7．3±s 1．2)和(7．5±1．0)h;cmax分别为(42±7)和(33±10)μg·L-1;t1／2分别为(13．7±2．0)和(12．5±2．2)h; MRT分别为(20±3)和(19．9±2．5)h;AUC0～72分别为(545±147)和(493±125)μg·h·L-1。氢氯噻嗪的tmax分别为(2．8±0．7)和(4．6±1．1)h;cmax分别为(82±23)和(77±13)μg·L-1;t1/2分别为(8．6±1．8)和(8．4±1．7)h;MRT分别为(10．4±2．0)和(11．6±1．6)h;AUC0～48分别为(680±281)和(684±83)μg·h·L-1。结论:该方法选择性强、灵敏度高、操作简便,适用于复方赖诺普利制剂的临床药动学研究;进食高脂肪、高蛋白的食物会影响赖诺普利的达峰浓度和氢氯噻嗪的达峰时间。更多还原

【Abstract】 AIM: To assess the effect of high protein and fat diet on the pharmacokinetic profiles of com- pound lisinopril and hydrochlorothiazide tablets (lisinopril, 10 mg; hydrochlorothiazide, 12.5 mg) by LC-MS. METHODS: The study was conducted according to an open, randomized, 2-period crossover design with a 1-week washout interval, which was administrated with a tablet of compound lisinopril and hydrochlorothiazide tablet on an empty stomach or after meal. The plasma concentrations of lisinopril and hydrochlorothiazide were measured by a fully validated LC-MS method. RESULTS: The major pharmacokinetic parameters of the single doses study on an empty stomach and after meal were as follows: for lisinopril-tmax were (7.3±s 1.2) vs (7.5±1.0) h; cmax were (42±7) vs (33±10)μg·L-1; t1/2 were (13.7±2.0) vs (12.5±2.2) h; MRT were (20±3) vs (19.9±2.5) h; AUC0-72 were (545±147) vs (493±125)μg·h·L-1, respectively. As for hydrochlorothiazide-tmax were (2.8±0.7) vs (4.6±1.1) h; cmax were (82±23) vs (77±13)μg·L-1; t1/2 were (8.6±1.8) vs (8.4±1.7) h; MRT were (10.4±2.0) vs (11.6±1.6) h; AUC0-48 were (680±281) vs (684±834)μg·h·L-1, respectively. CONCLUSION: LC-MS method is sensitive, convenient and proved to be suitable for clinical investigation of lisinopril and hydrochlorothiazide pharmacokinetics. High protein and fat diet could influence lisinopril’s cmax and hydrochlorothiazide’ s tmax.更多还原