恩扎卢胺软胶囊在中国健康男性受试者中的生物等效性研究

Bioequivalence of enzalutamide in healthy Chinese male healthy subjects

目的 研究恩扎卢胺软胶囊在中国健康男性受试者体内的生物等效性。方法 用单中心、随机、开放、两周期、两序列、双交叉、单次给药的试验方法设计。受试者空腹或餐后状态下口服受试或参比制剂160 mg后,用LC-MS/MS法检测恩扎卢胺的血药浓度,用WinNonlin 8.1计算药代动力学参数,并评价两制剂的生物等效性。结果 空腹试验入组29例受试者,28例完成试验。单剂量空腹试验的受试制剂和参比制剂恩扎卢胺的AUC_(0-72h)分别为(168 480.62±33 979.51)和(173 853.11±33 279.23) h·ng·mL^(-1),t_(max)别为1.00和1.25 h,C_(max)分别为(6 808.37±1 020.09)和(6 603.99±1 229.95) ng·mL^(-1);餐后试验入组28例受试者,27例完成试验,单剂量餐后给药受试制剂和参比制剂恩扎卢胺的AUC_(0-72h)分别为(174 218.28±35 093.48)和(174 597.58±31 421.57) h·ng·mL^(-1),t_(max)分别为2.50和2.50 h,C_(max)分别为(4 899.81±967.79)和(4 944.46±1 100.71) ng·mL^(-1)。空腹试验中受试制剂和参比制剂的C_(max)和AUC_(0-72h)几何均值比90%置信区间分别为97.86%~106.00%和95.20%~97.99%;餐后试验中受试制剂和参比制剂的C_(max)和AUC_(0-72h)几何均值比90%置信区间分别为93.50%~105.68%和97.50%~101.55%,均在80.00%~125.00%内。仅观察到空腹试验发生2例次可能与研究药物相关的不良事件。结论 在空腹和餐后状态下,2种恩扎卢胺软胶囊在中国健康男性受试者中具有生物等效性,且安全性良好。

Objective To investigate the pharmacokinetic parameters of enzalutamide and evaluate the bioequivalence in healthy Chinese male healthy subjects. Methods This was a single-center, randomized, open-label, two-period, two-sequence, crossover and single-administration trial. The blood concentration of enzalutamide was measured by LC-MS/MS after oral administration of 160 mg of the test or reference formulation in fasting or fed condition. Pharmacokinetic parameters were calculated using WinNonlin 8.1 and the bioequivalence of two formulations was evaluated by SAS 9.4 software. Results In the fasting condition, 29 subjects were enrolled and 28 completed. The major pharmacokinetic parameters were as follows, AUC_(0-72h)were(168 480.62±33 979.51) and(173 853.11±33 279.23) h·ng·mL^(-1);t_(max)were 1.00 and 1.25 h;C_(max)were(6 808.37±1 020.09) and(6 603.99±1 229.95) ng·mL^(-1), respectively. In the fed condition, 28 subjects were enrolled and 27 completed. The major pharmacokinetic parameters were as follows,AUC_(0-72h)were(174 218. 28 ± 35 093. 48) and(174 597. 58 ± 31 421. 57) h·ng·mL^(-1);t_(max)were 2. 50 and 2. 50h;C_(max)were(4 899. 81 ± 967. 79) and(4 944. 46 ± 1 100. 73) ng · mL^(-1), respectively. The 90% confidenceintervals of geometric mean ratio ofC_(max)and AUC_(0-72h)in the fasting state were 97. 86%-106. 00% and 95. 20%-97. 99%, and the 90% confidence intervals of geometric mean ratio of C_(max) and AUC_(0-72h) in the fed state were93. 50%-105. 68% and 97. 50%-101. 55%, respectively, which were in the bioequivalence range of 80. 00%-125. 00%. Only 2 cases of adverse events possibly related to the study drug in the fasting condition were observed.Conclusion The two formulations were shown to be bioequivalent in fasted and fed states in healthy Chinese malesubjects with a favorable safety profile.