Shao Da, Zhang Yi-Fan, Zhan Yan, Chen Xiao-Yan, Zhong Da-Fang
Yao Xue Xue Bao. 2014 Apr;49(4):524-9.
The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.
本研究旨在评估缬沙坦氢氯噻嗪片的生物等效性，并探究生物不等效的潜在原因。这是一项采用开放、随机双向交叉设计的单中心研究。将含160毫克缬沙坦和25毫克氢氯噻嗪的试验制剂和参比制剂给予36名健康男性志愿者。采用液相色谱-串联质谱法同时测定缬沙坦和氢氯噻嗪的血浆浓度。计算药代动力学参数和相对生物利用度，同时评估试验制剂和参比制剂之间的生物等效性。通过溶出度试验和高效液相色谱法测定试验制剂和参比制剂在四种不同介质中的溶出曲线。根据相似因子（f2）研究相似性。试验制剂中缬沙坦的F（o-t）和F（0-无穷大）分别为（139.4±65.2）%和（137.5±61.2）%。由此得出结论，试验制剂和参比制剂在缬沙坦方面生物不等效。在pH 1.2盐酸溶液的缬沙坦溶出度试验中，试验片和参比片之间观察到显著差异。生物不等效的关键因素可能是两种制剂中缬沙坦在酸性介质中的溶出存在明显差异。
