国产奥氮平片的人体药动学和生物等效性研究

 目的 评价国产奥氮平片在中国健康人体中的药动学及生物等效性。方法 采用双周期交叉试验设计，20名健康男性受试者单次口服国产和进口奥氮平片5 mg，采用LC-MS/MS测定奥氮平血药浓度，计算两制剂的主要药动学参数和生物利用度，并进行生物等效性评价。结果 国产和进口奥氮平片的主要药动学参数如下：t_max分别为(4.25±1.33)和(4.55±1.10) h，ρ_max分别为(9.62±1.79)和(9.69±2.18) ng·mL^-1，t_1/2分别为(31.71±6.87)和(32.46±5.67) h，AUC_0-t分别为(327.19±60.55)和(324.39±70.84) ng·h·mL^-1，AUC_0-∞分别为(354.44±74.58)和(350.70±80.94) ng·h·mL^-1。受试制剂的相对生物利用度F_0-t为（102.93±18.22）%，F_0-∞为（103.30±20.75）%，经统计分析，各药动学参数均无显著性差异(P>0.05)。结论 两种奥氮平制剂在体内过程相似，两制剂人体生物等效，临床上可以替换使用。

Pharmacokinetics and Bioequivalence of Domestic Olanzapine Tablets in Healthy Chinese Volunteers

OBJECTIVE To study the pharmacokinetics and bioequivalence of domestic olanzapine tablets in healthy Chinese volunteers. METHODS A single oral dose of 5 mg olanzapine tablets was given to 20 healthy male volunteers in a randomized cross-over study. The concentrations of olanzapine in plasma were determined by LC-MS/MS method. The pharmacokinetic parameters and relative bioavailability were calculated by DAS. Then the bioequivalence of two formulations was evaluated. RESULTS The pharmacokinetic parameters of domestic and imported formulations were as followst_max (4.25±1.33) and (4.55±1.10) h， ρ_max (9.62±1.79) and (9.69±2.18) ng·mL^-1， t_1/2 (31.71±6.87) and (32.46±5.67) h， AUC_0-t(327.19±60.55) and (324.39±70.84) ng·h·mL^-1， and AUC _0-∞ (354.44±74.58) and (350.70±80.94) ng·h·mL^-1， respectively. The relative bioavailability was （102.93±18.22）% for F_0-t and （103.30±20.75）% for F_0-∞. There was no significant difference between the two preparations (P>0.05). CONCLUSION The two preparations are bioequivalent and can be prescribed interchangeably.