盐酸普拉克索片在中国健康受试者的生物等效性试验

目的：研究盐酸普拉克索片与原研制剂森福罗的人体生物等效性。方法：24例健康受试者参加空腹试验，24例健康受试者参加餐后试验，均采用随机开放两周期交叉试验设计，分别于每周期单剂量口服0.25 mg盐酸普拉克索片受试制剂（T）或参比制剂（R）。采用液相色谱-串联质谱分析方法（LC-MS/MS）测定血浆中普拉克索浓度。用Phoenix WinNonlin 6.4计算药代动力学参数，其他统计分析工作使用SAS 9.3软件分析。结果：空腹组健康受试者口服受试制剂和参比制剂后的主要药代动力学参数（n=20）：Cmax分别为（481.15±102.21）、（497.25±133.31） pg/mL，Tmax分别为1.77（0.5,5）、1.50（0.5,5） h，AUC0-t分别为（6.18±1.49）、（6.20±1.28） pg·mL-1·h，AUC0-∞分别为（6.41±1.55）、（6.42±1.31） pg·mL-1·h，T1/2分别为（9.18±1.29）、（9.02±1.14） h。受试制剂Cmax、AUC0-t、AUC0-∞几何均数的90%置信区间分别落在参比制剂相应参数的92.20%～103.10%、94.06%～104.35%、94.17%～104.07%，均在80.00%～125.00%范围之间，符合生物等效性规定要求。高脂餐组健康受试者口服受试制剂和参比制剂后的主要药代动力学参数（n=22）：Cmax分别为（515.36±83.28）、（500.05±64.12）pg/mL，Tmax分别为2.00（1,4）、1.75（1,4）h，AUC0-t分别为（5.94±1.36）、（5.67±1.05）pg·mL-1·h，AUC0-∞分别为（6.16±1.43）、（5.88±1.11） pg·mL-1·h，T1/2分别为（8.92±2.00）、（8.85±1.98）h。受试制剂Cmax、AUC0-t、AUC0-∞几何均数的90%置信区间分别落在参比制剂相应参数的97.84%～107.41%、99.03%～108.79%、99.12%～108.68%，均在80.00%～125.00%范围内，符合生物等效性规定要求。结论：盐酸普拉克索片受试制剂和参比制剂在健康受试者体内具有生物等效性。

Bioequivalence study of pramipexole hydrochloride tablets in Chinese healthy subjects

AIM: To assess the bioequivalence of pramipexole hydrochloride tablets with reference(Sifrol). METHODS: A randomized, open-label, 2-period crossover study was conducted in 48 healthy Chinese volunteers under fasted or fed conditions (24 volunteers for each condition). In each session, the subjects received a single oral dose of 0.25 mg test (T) or reference (R) formulation. Pramipexole concentrations in plasma were determined by a validated HPLC-MS/MS. Pharmacokinetic parameters were calculated using a non-compartmental model through Phoenix WinNonlin version 6.4. Other statistic analysis were analyzed by using software of SAS 9.3. RESULTS: The pharmacokinetic parameters of test drug and reference drug under fasted condition(n=20) were: Cmax (481.15±102.21) and (497.25±133.31) pg/mL, Tmax 1.77 (0.5, 5) and 1.50 (0.5, 5) h, AUC0-t (6.18±1.49) and (6.20±1.28) pg·mL-1·h, AUC0-∞ (6.41±1.55) and (6.42±1.31) pg·mL-1·h, T1/2 (9.18±1.29) and (9.02±1.14) h, respectively. The 90%CIs of T/R for Cmax, AUC0-t and AUC0-∞ were 92.20%-103.10%, 94.06%-104.35%, 94.17%-104.07%, all were within the range of 80.00%-125.00%; the two formulations tested were considered bioequivalent when administered under fasted condition to healthy adult subjects. The pharmacokinetic parameters of test drug and reference drug under fedcondition (n=22) were: Cmax (515.36±83.28) and (500.05±64.12) pg/mL, Tmax 2.00 (1.00, 4.00) and 1.75 (1.00, 4.00) h, AUC0-t (5.94±1.36) and (5.67±1.05) pg·mL-1·h, AUC0-∞ (6.16±1.43) and (5.88±1.11) pg·mL-1·h, T1/2 (8.92±2.00) and (8.85±1.98) h, respectively. The 90%CIs of T/R for Cmax, AUC0-t and AUC0-∞ were 97.84%-107.41%, 99.03%-108.79%, 99.12%-108.68%, all were within the range of 80.00%-125.00%. All results meet the cretiria of bioequivance. CONCLUSION: This study suggests that the test formulation of pramipexole hydrochloride tablets are bioequivalent with the reference formulation of Sifrol in Chinese healthy subjects.