索他洛尔治疗心律失常的血药浓度与疗效的研究

Study on serum concentration and effects of sotalol in treatment of patients with arrhythmia

目的:观察索他洛尔(sotalol,S)治疗心律失常的疗效、副作用与血药浓度的关系。方法:选择门诊快速房性、室性心律失常患者100例,男53例,女47例。依次服用索他洛尔80、160、240mg·d-1,各2周,在每个剂量递增期的最后1d,分别于清晨服药前及服药后3h(即谷、峰浓度时)抽外周静脉血3ml,反相高效液相色谱荧光法(HPLC)测定索他洛尔的血药浓度,同时检查心电图测量QT、QTc间期、QTd以及动态心电图。结果:索他洛尔对室早的总有效率为85.7%,成对室早和短阵室速总有效率为73.3%、房性心律失常总有效率为70%,对预防阵发性房颤发作效果较好(P<0.05),而对持续性房扑、房颤以控制心室率较理想。索他洛尔治疗有效者平均有效药物浓度谷值为0.67±0.21mg·L-1,峰值1.33±0.51mg·L-1;无效者平均血药浓度谷值0.69±0.22mg·L-1,峰值1.36±0.53mg·L-1。结论:索他洛尔最佳剂量为160～240mg·d-1,副作用小,门诊应用较安全,持续用药可维持疗效,对房性及室性心律失常均有效。

AIM: To observe the relationship among the effects, side-effects and serum concentration of sotalol in treatment of patients with arrhythmia. METHODS: 100 cases (male 53, female 47) of out patient department (OPD) with atrial or ventricular arrhythmia were selected. Every different doses of sotalol (80, 160, 240 (mg·d^(-1))) were administrated two weeks in order. Samples of 3 ml peripheral venous blood were collected during the last day of the period of every different dose. The time of blood collecting was in the morning before administration and three hours after administration (i.e. peak and bottom serum concentration). RP-HPLC method was adopted. ECG (including QT, QTc episodes and QTd) and Holter examination were performed. RESULTS: Total efficiency of sotalol on arrhythmia: ventricular premature beats (VPB) was (85.7)%, couple VPB and paroxysmal ventricular tachycardia was (73.3)%, and atrial arrhythmia was 70%. The following results were still observed: better effects on the prevention to paroxysmal atrial fiberallation, ventricular rates being better controlled in atrial flutter and fiberallation. The average bottom value (ABV) of the effective serum concentration of the effective cases was (0.67)±(0.21) (mg·L^(-1)) and the peak value was (1.33)±(0.51) (mg·L^(-1)), but the ABV of the serum concentration was (0.69)±(0.22) (mg·L^(-1)) and peak value was (1.36)±(0.53) (mg·L^(-1)) in ineffective cases. CONCLUSION: The most rational doses of sotalol ranges between 160-240 (mg·d^(-1)) with some advantages, such as lower side effects, and effective to both atrial and ventricular arrhythmia.