高变异药物醋酸阿比特龙片人体生物等效性评价

目的: 评价高脂餐后单剂量口服高变异药物醋酸阿比特龙片受试制剂与参比制剂在中国健康人体中的生物等效性。方法: 本研究采用随机、开放、双序列、四周期重复四交叉试验设计，共入组健康男性受试者32人，单剂量高脂餐后口服受试制剂和参比制剂醋酸阿比特龙片250 mg。采用LC-MS/MS测定给药后血浆中阿比特龙药物浓度。使用WinNonlin 7.0计算药动学参数并用SAS 9.4软件进行生物等效性评价。结果: 受试制剂和参比制剂中阿比特龙C_max分别为(238.0±108.6）、(220.1±96.9) ng/mL，T _max分别为2.0(1.0-4.0)、2.0(1.0-5.0) h，t _1/2为(13.1±2.6)、(13.0±2.9) h，AUC _0-t 分别为(615.2±226.3)、(589.4±210.1) h·ng·mL^-1，AUC _0-∞分别为(618.7±227.7)、(592.8±211.6) h·ng·mL^-1。受试制剂和参比制剂阿比特龙的AUC _0-t 、AUC _0-∞和C _max的几何均数比值（T/R）的90%置信区间均在80.00%至125.00%范围内。结论: 醋酸阿比特龙片受试制剂与参比制剂在餐后给药时具有生物等效性。

Bioequivalence of high variation drug abiraterone acetate tablets in healthy subjects

AIM: To evaluate the bioequivalence of the experimental preparation and reference preparation of the high-variation drug abiraterone acetate tablets administered once orally in the healthy Chinese volunteers after taking fatty food. METHODS: It was a randomized, open-label, double- sequence, four-period, repeated cross-test and 32 healthy volunteers were given a single oral 250 mg dose of test or reference abiraterone acetate tablets with a high-fat meal. The blood concentrations of abiraterone in plasma were determined by LC-MS/MS. The major pharmacokinetic parameters were calculated with the aid of WinNonlin 7 and the bioequivalence was evaluated. RESULTS:The abiraterone's major pharmacokinetic parameters of test and reference were as follows: C _max were（238.0±108.6）and（220.1±96.9）ng/mL; T _max were 2.0 (1.0-4.0) and 2.0 (1.0-5.0) h; t _1/2 were (13.1±2.6) and (13.0±2.9) h; AUC _0-t were (615.2±226.3) and (589.4±210.1) h·ng·mL^-1， AUC _0-∞ were (618.7±227.7) and (592.8±211.6) h·ng·mL^-1, respectively. The 90% confidence interval, the geometric mean ratio（T/R）of the AUC _0-t ,AUC _0-∞ and C _max, all ranged from 80.00% to 125.00%. CONCLUSION: The test preparation of acetabone acetate tablets is bioequivalent to the reference preparation after diet.