酒石酸美托洛尔缓释微丸和缓释片在健康人体内的药动学比较

In Vivo Pharmacokinetic Comparison of Metoprolol Tartrate Sustained-Release Pellets and Tablets in Healthy Persons

目的研究酒石酸美托洛尔缓释微丸和缓释片在人体的药动学特征,评价两者的生物等效性。方法选择18～40岁健康成年男性12名,采用双周期双交叉试验设计,健康志愿者分别口服酒石酸美托洛尔缓释微丸和缓释片,应用高效液相-荧光检测方法测定经时血药浓度,应用DAS软件计算药动学参数。结果酒石酸美托洛尔缓释微丸和缓释片的药动学参数,峰浓度(Cmax)为(70.12±37.43)ng/mL和(63.93±38.59)ng/mL,达峰时间(Tmax)为(4±0)h和(4±0)h,消除相半衰期(t1/2)为(4.60±0.77)h和(6.16±2.11)h,0-t药时曲线下面积(AUC0-t)为(666.35±541.36)ng/(mL.h)和(630.19±487.83)ng/(mL.h),0-∞药时曲线下面积(AUC0-∞)为(747.15±575.05)ng/(mL.h)和(715.88±499.18)ng/(mL.h),平均驻留时间(MRT)为(9.43±1.14)h和(10.31±2.51)h,相对生物利用度(F)为(103.0±31.1)%。结论制备的酒石酸美托洛尔缓释微丸与市售制剂酒石酸美托洛尔缓释片相比具有生物等效性。

Objective To study the in vivo pharmacokinetic characteristics of metoprolol tartrate sustained-release pellets（T） and tablets（R）,and to evaluate their bioequivalence.Methods By using the double-blind,double-cross trial design,12 healthy male adults aged 18-40 years old were selected and orally took the test sustained-release pellets and reference ustained-release tablets.The serum concentrations of metoprolol tartrate were measured in 24 h after the administration by HPLC-fluorescence method.The pharmacokinetic parameters were calculated by using DAS software.Results The pharmacokinetic parameters and the peak concentrations of the pellets and tablets were：Cmax（70.12±37.43 ng/mL） and（63.93±38.59 ng/mL）,Tmax（4±0 h） and（4±0 h）,T1/2（4.60±0.77 h） and（6.16±2.11 h）,AUC0-t（666.35±541.36 ng/mL·h） and（630.19±487.83 ng/mL·h）,AUC0-∞（747.15±575.05 ng/mL·h） and（715.88±499.18 ng/mL·h）,MRT（9.43±1.14 h） and（10.31±2.51 h）,respectively.The relative bioavailability（F）of the pellets and tablets was（103.0±31.1）%.Conclusion The prepared metoprolol tartrate sustained-release pellets is bioequivalent to the market metoprolol sustained-release tablets.