厄贝沙坦氢氯噻嗪片中氢氯噻嗪人体生物等效性研究

Study on Biequivalence of Hydrochlorothiazide in Irbesartan and Hydrochlorothiazide Tablets

目的:评价两种复方厄贝沙坦片中氢氯噻嗪的生物等效性。方法:20名健康男性志愿者分别单剂量po受试制剂和参比制剂,采用高效液相色谱-质谱联用法测定血浆中氢氯噻嗪的浓度并拟合药动学参数。结果:受试制剂和参比制剂在受试者体内的药动学参数如下:血浆中氢氯噻嗪的C_(max)(72.6±33.8)和(74.7±31.9)ng·ml^(-1),t_(max)(2.0±0.5)和(1.8±0.4)h,t_(1/2)(2.9±1.2)和(2.5±1.0)h,AUC_(0-48h)(372.3±168.7)和(377.5±210.4)ng·h·ml^(-1),AUC_(0-∞)(398.3±191.2)和(396.5±223.5)ng·h·ml^(-1)。与参比制剂相比,受试制剂中氢氯噻嗪的平均相对生物利用度为(106.7±26.1)%。结论:两种制剂中氢氯噻嗪具生物等效性。

Objective： To develop the LC-MS method for assay of hydroehlorothiazide in human plasma and to conduct bioequivalenee study of compound irbesartan and hydrochlorothiazide tablets in human. Method： A single oral dose of compound irbesartan and hydrochlorothiazide tablets was given according to a randomized crossover design. The plasma concentation of hydrochlorothiazide were determined by a high performance liquid chromatography-mass spectrometry method. Result： The main pharmacokinetic parameters of the test and the reference tablets were as follows ： Cmax were （72.6 ± 33.8 ） and （ 74.7 ± 31.9 ） ） ng· ml^-1, tmax were （ 2.0 ± 0.5 ） and （1.8 ± 0.4） h,tl/2were （2.9 ± 1.2） and （2.5 ± 1.0） h,AUCo-48hwere （372.3 ± 168.7） and （377.5 ± 210.4） ng-h·ml^-1, AUCo0-∞ were （398.3 ±191.2） and （396.5 ± 223.5） ng·ml^-1, respectively. The relative bioavailabiliry of the test formulation was （ 106.7 ± 26.1 ） %. Conclusion ： The test compound tablets were bioequivalence to the reference tablets.