索他洛尔的药动学及其血药浓度与QTc延长的关系

Pharmacokinetics and pharmacodynamics of sotalol in healthy volunteers

目的：为研究国产索他洛尔的药动学及其QTc延长与血药浓度之间的关系。方法：6名健康志愿者口服国产索他洛尔单剂160 mg后分别于0，0.5，1.5，2，3，3.5 ，4，6，8，12，24，36 h抽血及行心电图检查。采用反相高效液相色谱-荧光检测法检 测血清中索他洛尔的浓度，根据QTc=QT/RR1/2得到相应的QTc值。结果：国产索他洛尔片剂AUC，Cmax，Tmax，T1/2β分别为（ 17.3±2.3） μg·ml-1·h,（1.27±0.21） μg·ml-1， （2.3±0.6） h，（11.3±1.1） h。索他洛尔产生的QTc延长与血药浓度成线性相关， 并可见最大QTc延长滞后于血药浓度。结论：国产索他洛尔在国人体内的药动学参数与西方人相近，索他洛尔产生的QTc延长与血药浓度 成线性相关，最大QTc延长滞后于血药浓度。

OBJECTIVE To study the pharmacokinetics and the relation of QTc prolongation with serum le vel of domestic sotalol tablets. METHODS After a single oral dose of 160mg of sotalol,serum specimen was drawn and ECG w as performed in 6 healthy male volunteers at 0,0.5,1.5,2,3,3.5,4,6, 8,12,24,36 h.The serum levels of sotalol were assayed by high performance liquid chromatography with fluorescence detection.QTc value was calculated by the form ula QTc=QT/RR1/2. RESULTS The pharmacokinetic parameters of the sotalol tablets were:AUC (17.3±2.3) μg·ml-1·h;Cmax (1.27±0.21) μg·ml-1;Tmax (2.3±0.6) h;T1/2β (11.3±1.1) h,respectively.There was a significant linear relation between the average QTc and the mean sotalol concent ration in serum obtained at the corresponding time.A hysteresis of QTc prolonga tion was also observed. CONCLUSIONS The pharmacokinetic parameters of domestic sotalol in Chinese are like as the we stern population.There are a hysteresis of QTc prolongation and a significant li near relation between the average QTc and the mean sotalol concentration in seru m.