Study on Pharmacokinetics of compound lisinopril and hydrochlorothiazide tablets in healthy human volunteers

OBJECTIVE To assess the pharmacokinetic profiles of compound lisinopril and hydrochlorothiazide tablets by LC-MS.METHODS The single dose study was conducted in 12 healthy volunteers with a tablet of compound lisinopril and hydrochlorothiazide tablets(10 mg/12.5 mg);The multiple dose study was performed in 12 healthy volunteers with a tablet of compound lisinopril and hydrochlorothiazide tablets for 9 days.The plasma concentrations of lisinopril and hydrochlorothiazide were measured by a fully validated LC-MS method.RESULTS The major pharmacokinetic parameters of the single dose study on an empty stomach were as follows: For Lisinopril tmax(7.3±1.2) h;Cmax(42.5±6.8) μg·L-1;t1/2(8.6±1.8) h;MRT(20.1±3.0);AUC0-72(545.1±147.4) ng·h·L-1,respectively.As for hydrochlorothiazide,tmax(2.8±0.7)h;Cmax(81.6±22.7)μg·L-1;t1/2(13.7±2.0)h;MRT(10.4±2.0);AUC0-48(679.8±280.7)ng·h·L-1,respectively.Major pharmacokinetic parameters for multiple doses were as follows: for lisinopril,AUCss(576.9±124.4) ng·h·L-1,Css-max(47.7±13.2) μg·L-1,Css-min(6.2±1.8) μg·L-1,Css-av(24.0±5.2) μg·L-1,DF(1.71±0.24),tmax(7.3±1.1) h,t1/2(13.1±2.7) h,respectively;for hydrochlorothiazide,AUCss(731.4±224.9) ng·h·L-1,Css-max(101.0±31.6) μg·L-1,Css-min(8.4±3.8)μg·L-1,Css-av(30.5±9.4)μg·L-1,DF(3.1±1.2),tmax(3.0±0.9) h,t1/2(8.8±1.6) h,respectively.CONCLUSION There is no significant difference in pharmacokinetic parameters of compound lisinopril and hydrochlorothiazide tablets (10 mg/12.5 mg) between single and multiple administration,no accumulation after administration.