国产佐米曲坦片药动学及生物等效性研究

 目的在中国健康成年男性志愿者中比较研究国产和进口佐米曲坦片剂的药动学参数,评估两者的生物等效性。方法24名健康男性受试者随机交叉给药,分别单剂口服国产和进口佐米曲坦片7.5mg。以HPLC测定血药浓度,应用3P97软件计算两者的药动学参数并考察其生物等效性。结果受试者按自身前后交叉设计分别应用国产片剂(试验制剂)和进口片剂(参比制剂)7.5mg后,药-时曲线符合一房室模型,主要药动学参数:t_max分别为(2.48±0.40)和(2.50±0.36)h;ρ_max分别为(13.22±2.55)和(13.06±3.24)μg.L^-1;AUC_0-t分别为(59.52±19.99)和(63.60±17.98)μg.h.L^-1;t_1/2ke分别为(2.16±0.62)和(2.31±0.50)h;国产片剂对于进口片剂的相对生物利用度为(94.8±13.0)%,两种片剂的AUC_0-t及ρ_max经双向单侧t检验表明,AUC_0-t和ρ_max90%置信区间分别为89.1%～97.7%和95.1%～104.0%,根据本试验结果,可判定两种制剂生物等效。结论国产与进口佐米曲坦片剂为生物等效制剂。

Pharmacokinetics and Bioequivalence of Domestic Zolmitriptan Tablets in Chinese Healthy Volunteers

OBJECTIVE To study pharmacokinetics and bioequivalence of domestic and imported zolmitriptan tablets in Chinese healthy volunteers. METHODS A single oral dose of 7.5 mg domestic and imported zolmitriptan tablets was given to 24 healthy volunteers in a randomized cross-over study. The concentrations of zolmitriptan in human plasma were determined by HPLC and the pharmacokinetic parameters were calculated by 3P97 software.RESULTS The concentration-time curves of zolmitriptan in plasma werefitted with a two compartment model after an oral single dose.The main pharmacokinetic parameters of domestic and imported tablet were as follows:t_max (2.48±0.40) and (2.50±0.36)h , ρ_max (13.22±2.55) and (13.06±3.24)μg·L^-1,AUC_0-t(59.52±19.99) and (63.60±17.98)μg·h·L^-1, t_1/2ke (2.16±0.62) and (2.31±0.50)h,respectively. The relative bioavailability of zolmitriptan was (94.8±13.0)%. Statistical analysis showed that domestic and imported zolmitriptan were bioequivalent, the 90% confidence interval of AUC_0-t and ρ_max were 89.1%～97.7% and 94.9%～111.0%,respectively. CONCLUSION The domestic and imported zolmitriptan tablets are bioequivalent.