Gascón A R, Cuadrado A, Solinís M A, Hernández R M, Ramírez E, Dalmau R, Pedraz J L
Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Txagorritxu Hospital, Vitoria, Spain.
Int J Clin Pharmacol Ther. 2003 Jul;41(7):309-15. doi: 10.5414/cpp41309.
Two formulations of lisinopril/hydrochlorothiazide (20 mg/12.5 mg) were evaluated for bioequivalence after single dosing in healthy volunteers.
The study was conducted according to an open, randomized, 2-period crossover design with a 2-week washout interval between doses. Twenty-four volunteers participated and all completed the study successfully. Lisinopril and hydrochlorothiazide were determined in plasma by HPLC. The pharmacokinetic parameters AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were tested for bioequivalence after logarithmic transformation of data and ratios of tmax were evaluated non-parametrically.
For lisinopril, the parametric analysis revealed the following test/reference ratios and their confidence intervals (90% CI): 1.01 (0.84-1.22) for AUC(0-t), 0.98 (0.81-1.19) for AUC(0-infinity), 1.02 (0.83-1.25) for Cmax and 1.03 (0.99-1.08) for Cmax/AUC(0-infinity). The 90% CI for tmax was 0.94-1.07. All parameters showed bioequivalence between both formulations. As for hydrochlorothiazide, test/reference ratios and their confidence intervals (90% CI) were: 1.05 (0.95-1.17), 1.02 (0.93-1.12) for AUC(0-infinity), 0.99 (0.89-1.07) for Cmax and 0.97 (0.90-1.04) for Cmax/AUC(0-infinity). The 90% CI for tmax was 1.00-1.41. All parameters showed bioequivalence between both formulations except for tmax. A discrete fall in both systolic (SBP) and diastolic (DBP) blood pressure was observed after drug administration. The time course of both parameters was similar for the 2 formulations. Heart rates also followed a similar time profile.
The bioequivalence of the 2 formulations of lisinopril/hydrochlorothiazide was demonstrated.
在健康志愿者单次给药后，对两种赖诺普利/氢氯噻嗪制剂（20毫克/12.5毫克）的生物等效性进行评估。
该研究按照开放、随机、两周期交叉设计进行，剂量之间有两周的洗脱期。24名志愿者参与并全部成功完成研究。通过高效液相色谱法测定血浆中的赖诺普利和氢氯噻嗪。对数据进行对数转换后，测试药代动力学参数AUC(0 - t)、AUC(0 - ∞)、Cmax和Cmax/AUC(0 - ∞)的生物等效性，并对tmax比值进行非参数评估。
对于赖诺普利，参数分析显示以下测试/参比制剂的比值及其置信区间（90%CI）：AUC(0 - t)为1.01（0.84 - 1.22），AUC(0 - ∞)为0.98（0.81 - 1.19），Cmax为1.02（0.83 - 1.25），Cmax/AUC(0 - ∞)为1.03（0.99 - 1.08）。tmax的90%CI为0.94 - 1.07。所有参数均显示两种制剂具有生物等效性。至于氢氯噻嗪，测试/参比制剂的比值及其置信区间（90%CI）为：AUC(0 - ∞)为1.05（0.95 - 1.17）、1.02（0.93 - 1.12），Cmax为0.99（0.89 - 1.07），Cmax/AUC(0 - ∞)为0.97（0.90 - 1.04）。tmax的90%CI为1.00 - 1.41。除tmax外，所有参数均显示两种制剂具有生物等效性。给药后观察到收缩压（SBP）和舒张压（DBP）均有明显下降。两种制剂这两个参数的时间进程相似。心率也呈现相似的时间变化趋势。
证实了两种赖诺普利/氢氯噻嗪制剂的生物等效性。
