比卡鲁胺胶囊与片剂健康人体生物等效性研究

目的:研究比卡鲁胺胶囊(试验制剂)与比卡鲁胺片(参比制剂)在健康人体内的药动学特征,评价2种制剂生物等效性。方法:48名健康志愿者,随机分为2组,采用单周期平行试验设计,单剂量口服比卡鲁胺试验制剂或参比制剂50 mg,采用高效液相色谱法测定给药前和给药后不同时间点血浆中比卡鲁胺浓度,计算试验制剂和参比制剂的药动学参数。同时对比卡鲁胺主要药动学参数进行方差分析、双单侧t检验和(1-2α)置信区间分析,评价试验制剂和参比制剂的生物等效性。结果:比卡鲁胺试验制剂和参比制剂主要药动学参数分别为t_(1／2)(138±s 32)和(146±27)h,t_(max)(17±5)和(17±5)h, c_(max)(911±130)和(869±115)μg·L~(-1),AUC_(0～672)(172437±39863)和(17684．2±35734)μg·h·L~(-1), AUC_(0～∞)(179457±43128)和(185270±39689)μg·h·L~(-1)。c_(max),AUC_(0～672)和AUC_(0～∞)置信区间分别为98．9%～100．7%,98．8%～100．6%和99．7%～101．7%。结论:比卡鲁胺胶囊相对生物利用度为97．51%。比卡鲁胺试验制剂和参比制剂具有生物等效性。

Bioequivalence of bicalutamide capsules and tablets in Chinese healthy volunteers

AIM:To establish a HPLC method for the determination of bicalutamide plasma concentration and to evaluate the bioequivalence of bicalutamide capsules(test)and tablets(reference).METHODS:A single oral dose of 50 mg bicalutamide capsules or tablets were given to 48 Chinese healthy volunteers in a one period parallel design test.The plasma concentrations of bicalutamide were determined by HPLC method and the pharmacokinetic parameters of bicalutamide test and reference were calculated and the bioequivalence was evaluated with DAS 2.0.RESULTS:The main pharmacokinetic parameters of bicalutamide test and reference were as follows,t_(1/2),(138±s 32)and(146±27)h,t_(max),(17±5)and(17±5)h,c_(max),(911±130) and(869±115)μg·L~(-1),AUC_(0-672),(172437±39863)and(176842±35734)μg·h·L~(-1),AUC_(0-∞), (179457±43128)and(185270±39689)μg·h·L~(-1),respectively.The two-one side t-test analysis showed that the confidence intervals of c_(max),AUC_(0-672)and AUC_(0～∞)were 98.9%-100.7%,98.8%-100.6% and 99.7%-101.7%,respectively.CONCLUSION:The relative bioavailability of bicalutamide capsules was 97.51% and the pharmacokinetic parameters of bicalutamide test and reference show no statistical difference and the two-one side t-test shows that they are bioequivalent.