Study on Pharmacokinetics of Compound Lisinopril Tablets in Chinese Volunteers

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.