比卡鲁胺片在中国健康志愿者中的生物等效性研究

Bioequivalence of bicalutamide tablets in healthy Chinese volunteers

目的:评价比卡鲁胺片(50 mg)在中国健康成年男性志愿者体内药动学特征及国产受试制剂与参比制剂(康士得^(?))的生物等效性。方法:空腹与餐后试验各入组40例健康志愿者,采用随机开放两周期两序列交叉试验设计,志愿者两周期分别服用50 mg比卡鲁胺片受试制剂或参比制剂,清洗期为56 d,采集给药后576 h内的血样,采用液相色谱-串联质谱法(LC-MS/MS)测定EDTA-K2人血浆中比卡鲁胺浓度,采用非房室模型计算药动学参数,根据C_(max),AUC_(0-t),AUC_(0-∞)几何均值比值(GMR)90%置信区间(CI)是否在80.00%~125.00%范围内判断两制剂生物等效性。结果:空腹状态下比卡鲁胺片受试制剂与参比制剂药动学参数C_(max)分别为(1 030±196)和(898±167) ng·mL^(-1),AUC_(0-t)分别为(224 000±42 900)和(196 000±48 400) h·ng·mL^(-1),AUC_(0-∞)分别为(243 000±56 900)和(212 000±60 100) h·ng·mL^(-1),餐后状态下比卡鲁胺片受试制剂与参比制剂药动学参数C_(max)分别为(1 260±164)和(1 210±153) ng·mL^(-1),AUC_(0-t)分别为(245 000±40 700)和(241 000±44 700) h·ng·mL^(-1),AUC_(0-∞)分别为(266 000±55 700)和(259 000±57 000) h·ng·mL^(-1)。空腹及餐后条件下C_(max),AUC_(0-t),AUC_(0-∞)的几何均值比值90%CI均在80.00%~125.00%等效范围内。试验过程无严重不良事件发生。结论:在空腹及餐后状态下,比卡鲁胺片受试制剂与参比制剂生物等效,安全性良好。

Objective:To analyze the pharmacokinetics of bicalutamide(50 mg) in healthy Chinese male volunteers and to evaluate the bioequivalence of domestic generic and reference bicalutamide(CASODEX~?) in healthy Chinese male volunteers.Methods:A randomized,open,two-cycle,two-sequence,and cross-over study with a 56-day washout period was conducted under fasting and postprandial conditions in healthy Chinese male volunteers(40 subjects/condition).Eligible subjects randomly received a single 50 mg dose of either the test or the reference formulation.A serial blood samples were collected over a 576-hour interval following drug administration.The concentrations of bicalutamide in EDTA-K2 human plasma were determined by the liquid chromatography-tandem mass spectrometry(LC-MS/MS) method,with non-compartmental model used for pharmacokinetic analysis.The bioequivalence of the two preparations was determined according to whether the 90% confidence interval(CI) of C_(max),AUC_(0-t) and AUC_(0-∞) geometric mean ratio was within the range of 80.00%~125.00%.Results:The pharmacokinetic parameters of the test and reference capsules under fasting condition are as follows:C_(max)(1 030±196) and(898±167) ng·mL^(-1);AUC_(0-t)(224 000±42 900) and(196 000±48 400) h·ng·mL^(-1),AUC_(0-∞)(243 000±56 900) and(212 000±60 100) h·ng·mL^(-1).The pharmacokinetic parameters of the test and reference capsules under fed condition are as follows:C_(max)(1 260±164) and(1 210±153) ng·mL^(-1);AUC_(0-t)(245 000±40 700) and(241 000±44 700) h·ng·mL^(-1);AUC_(0-∞)(266 000±55 700) and(259 000±57 000) h·ng·mL^(-1).The 90% confidential intervals of the GMRs of C_(max),AUC_(0-t) and AUC_(0-∞) fall within bioequivalence criteria(80.00%~125.00%).No serious adverse event was observed.Conclusion:The domestic bicalutamide formulation is bioequivalent to the reference formulation CASODEX~?.Both formulations are generally well tolerated.