琥珀酸美托洛尔缓释片在中国人体的药动学特性

目的研究琥珀酸美托洛尔缓释片在中国人体的药动学特性.方法采用HPLC荧光检测法测定血浆中美托洛尔的浓度.结果22名健康受试者口服单剂量50mg琥珀酸美托洛尔缓释片后的AUC0-t为(173.15±99.52)μg·h·L-1,AUC0-∞为(237.44±162.11)μg·h·L-1,cmax为(15.67±7.69)μg·L-1,tmax为(6.14±2.55)h,MRT为(14.17±4.01)h;多剂量口服50mg缓释片后的AUCss0-t为(335.42±235.19)μg·h·L-1,cmax为(23.03±15.16)μg·L-1,tmax为(5.8±2.2)h,cmin(6.73±4.98)μg·L-1,平均稳态血药浓度cav是(13.98±9.80)μg·L-1,血药浓度波动度DF(%)(122.55±53.93)%.结论单剂量给予缓释片的结果与美托洛尔普通片相比,tmax明显延长(5.8vs 1.1 h),cmax明显降低(15.67×2vs 186.2μg·L-1).琥珀酸美托洛片缓释片与普通片相比在中国健康受试者中的缓释特征明显,安全性良好.在整个试验过程中监测血压、心率,无低血压、血晕等不良反应发生.

Pharmacokinetics of a metoprolol prolonged-release tablet in Chinese healthy volunteers

AIM: To evaluate the safety and pharmacokinetic parameters of a metoprolol prolonged-release tablet in healthy Chinese volunteers. METHODS: Twenty-two healthy Chinese volunteers were given a single and multiple oral dose 50 mg of metoprolol prolonged-release tablet. The concentration of metoprolol in blood plasma was measured by an validated HPLC fluorescence method and was assessed with non-compartment model to obtain the pharmacokinetic parameters. RESULTS: The pharmacokinetic parameters of metoprolol prolonged-release formulation for orally administered (122.55 +53.93)% after multiple doses. CONCLUSION: The results show that tmax(5.8 vs 5 h) is similar in Chinese volunteers with that as reports in caucasuians,but cmax(23.3vs 48.62 μg·L-1), Cmin(6.73 vs 26.71 μg·L-1) and DF are different after multiple doses. Tmax(5.8 vs 1.1 h),cmax(15.67 x 2 vs 186.2 μg·L-1) of metoprolol prolongedrelease tablet are significantly different with those of the conventional tablet of metoprolol after single dose in Chinese volunteers.No any adverse drug reactions such as hypotension,dizziness,etc occur during the whole study.