【摘要】 目的研究健康志愿者口服复方赖诺普利片后赖诺普利和氢氯噻嗪的药动学过程。方法采用双交叉试验设计,12名健康志愿者单剂量分别空腹和进食后口服复方赖诺普利片1片(每片含赖诺普利10.0mg、氢氯噻嗪12.5mg),多剂量连续口服复方赖诺普利片9d,每天1片,采用LC-ESI-MS测定赖诺普利和氢氯噻嗪的血药浓度,计算药动学参数。结果单剂量分别空腹和进食后口服复方赖诺普利片1片后赖诺普利的ρmax分别为(42.5±6.8)和(33.0±10.4)μg·L-1;氢氯噻嗪的tmax分别为(2.8±0.7)和(4.6±1.1)h,其余药动学参数不受进食影响。多剂量连续口服复方赖诺普利片后赖诺普利的ρss-av为(24·0±5.2)μg·L-1,DF为(1.71±0.24),R为(1.60±0.36);氢氯噻嗪的ρss-av为(30.5±9.4)μg·L-1,DF为(3.12±1.21),R为(1.22±0.23)。结论和空腹服药相比较,饮食影响复方赖诺普利片中的赖诺普利的达峰浓度和氢氯噻嗪的达峰时间。赖诺普利和氢氯噻嗪在健康受试者体内不存在蓄积现象。更多还原

【Abstract】 OBJECTIVE To investigate the pharmacokinetics of lisinopril and hydrochlorothiazide in healthy volunteers.METHODS According to a randomized two-crossover design,12 volunteers received a single oral dose of compound lisinopril tablet(containin 10 mg lisinopril and 12.5 mg hydrochlorothiazide) while fasting and immediately after consumption of a meal respectively.After the single dose design,the volunteers participated in the multiple dose design.Each volunteer received a piece of compound lisinopril tablet per day for nine consecutive days.The concentrations of lisinopril and hydrochlorothiazide in human plasma were determined by LC-ESI-MS methods.RESULTS ρmax of lisinopril were(42.5±6.8) and(33.0±10.4) μg·L-1 after a single dose while fasting and fed state;tmax of hydrochlorothiazide were(2.8±0.7) and(4.6±1.1) h after a single dose while fasting and fed state.The main pharmacokinetic parameters of lisinopril and hydrochlorothiazide in multiple doses were as follows:ρss-av were(24.0±5.2) and(30.5±9.4)μg·L-1,DF were(1.71±0.24) and(3.12±1.21),R were(1.60±0.36) and(1.22±0.23).CONCLUSION Compared with after meal,ρmax of lisinopril decreased and tmax of hydrochlorothiazide delayed while fasting.There was no accumulation of lisinopril and hydrochlorothiazide in vivo after multiple oral doses of compound lisinopril tablets for 9 d.更多还原