十名志愿者口服维拉帕米缓释片药代动力学和心电图研究

对10名男性受试者单剂量po240mgVer缓释片药代动力学及心电图变化进行研究。血药浓度—时间数据用零级吸收过程的一室模型拟合,其药代动力学参数:T_max5.9±1.6h;C_max118.9±37.2μg·L^-1;T₁ 5.4±1.5h;k₀30.5±17.5μg·L^-1·h^-1;T_1/210.8±4.9h。PR间期延长有显著意义,血药浓度与PR间期变化满足S 型模型,其药效学参数:EC₅₀ 64.6±16.9μg·L^-1; E_max54±11ms;s 1.68±0.66。

PHARMACOKINETIC AND ELECTROCARDIOGRAPHIC STUDY OF ORAL VERAPAMIL SUSTAINED RELEASE TABLET IN 10 CHINESE VOLUNTEERS

Both verapamil pharmacokinetics and electrocardio graphic changes in 10 Chinese volunteers were studied after po 240 mg of verapamil sustained release tablet. A one compartment model with zero order absorption gave a better fitting to concentration-time data with values of r²>0.96. The main pharmacokinetic parameters obtained were: T_max, 5.9±1.6 h; C_max, 118.9±37.2 μg·5L^-1 ; T₁, 5.4±1.5 h; k₀, 30.5±17.5 μg·5L^-1 \5h -1 ; T_1/2, 10.8 ±4.9 h; MRT, 15.4±3.2 h and AUC. 1.96±0.82 mg·5h·5L^-1 . There were significant prolongations of PR intervals after dose. Relationships between PR interval changes and plasma concentrations of verapamil were better fitted to sigmoidal model, with r²>0.98. The corresponding pharmacodynamic parameters were estimated. EC₅₀ , 64.6±16.9 μg·5L^-1 , E_max, 54±11 ms and s, 1.68±0.66.