Suppression of resistant ventricular arrhythmias by twice daily dosing with flecainide.
Suppression of resistant ventricular arrhythmias by twice daily dosing with flecainide.
复制标题
每日两次服用氟卡尼可抑制难治性室性心律失常。
DOI：
10.1016/0002-9149(81)90331-3
复制
发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Woosley,RL
中科院分区：
文献类型：
--
作者：
Duff,HJ;Roden,DM;Maffucci,RJ;Vesper,BS;Conard,GJ;Higgins,SB;Oates,JA;Smith,RF;Woosley,RL
醋酸氟卡胺是一种新的抗心律失常药物，其药代动力学表明，每日两次给药可获得有效的治疗效果。观察氟卡胺对11例慢性室性早搏患者的抗心律失常和心电图疗效。9名患者对至少三种抗心律失常药物有抵抗或不耐受，8名患者有反复发作的非持续性室性心动过速。通过与增加剂量前2天和增加剂量后3天服用安慰剂的结果比较，确定增加剂量氟卡胺的抗心律失常效果。11例患者均有抗心律失常反应，每日平均剂量为410 mg(200~600 mg)的氟卡胺对室性早搏的抑制率平均为97%(88~100)，室性心动过速的抑制率平均为100%。有效的治疗伴随着P-R间期(+29%)、QRS间期(+27%)和Q-TC间期(+11%)的延长。这些变化与二维超声心动图评估的运动耐量恶化或射血分数降低(安慰剂组0.52±0.08，氟卡胺组0.53±0.12)无关。氟卡胺剂量的增加与室性早搏抑制前室性偶联间期的逐渐延长有关。在多次口服后的安慰剂洗脱期内，氟卡胺的终末(吸收后)相血浆半衰期为13-27小时(平均20.3小时)。氟卡胺的最低有效血浆浓度(导致超过90%的室性早搏抑制)范围为245至980 ng/ml(平均值631)。在住院评估期间，不良反应仅限于3名患者视力模糊，但用较小但仍然有效的剂量解决了这一问题。在门诊治疗期间，室性异位搏动的平均抑制率为95%。在对9名患者进行的平均12个月的门诊随访中，对动态心律失常频率的定期评估继续证明心律失常得到抑制。门诊随访在前6个月按月进行，此后每2个月进行一次。在三名患者中，每8小时给药一次是必要的，因为在每12小时给药一次时，血浆浓度达到峰值时就会出现视力模糊。氟卡胺每天给药两次，在抑制室性心律失常方面非常有效。
Flecainide acetate is a new antiarrhythmic agent whose pharmacokinetics have suggested that effective therapy could be achieved with twice daily dosing. The antiarrhythmic and electrocardiographic effects of flecainide were evaluated in 11 patients with chronic ventricular ectopic beats. Nine patients had been resistant or intolerant to at least three antiarrhythmic agents and eight had recurrent nonsustained ventricular tachycardia. The antiarrhythmic efficacy of increasing doses of flecainide was determined by comparison with results during administration of a placebo 2 days before and 3 days after increasing doses of flecainide. All 11 patients had an antiarrhythmic response with a mean 97 percent (range 88 to 100) rate of suppression of ventricular ectopic beats and mean 100 percent rate of suppression of ventricular tachycardia with a mean daily dose of 410 mg (range 200 to 600) of flecainide. Effective therapy was accompanied by lengthening of the P-R (+ 29 percent), QRS (+ 27 percent) and Q-Tc (+ 11 percent) intervals. These changes were not associated with a deterioration in exercise tolerance or a reduction in ejection fraction (0.52 ± 0.08 with placebo, 0.53 ± 0.12 with flecainide) as assessed with two dimensional echocardiography. Increasing doses of flecainide were associated with progressive prolongation of the ventricular ectopic coupling interval before suppression of ventricular ectopic beats. During the placebo washout period after multiple oral doses, the terminal (postabsorptive) phase plasma half-life of flecainide was found to range from 13 to 27 hours (mean 20.3). The minimal effective plasma levels of flecainide (resulting in greater than 90 percent suppression of ventricular etopic beats) ranged from 245 to 980 ng/ml (mean 631). Adverse effects during the inpatient evaluation were limited to blurring of vision in three patients, which resolved with smaller but still effective doses.Suppression of ventricular ectopic beats at a mean rate of 95 percent continued during outpatient therapy. During a mean of 12 months of outpatient follow-up in nine patients, regularly scheduled evaluation of ambulatory arrhythmia frequency continued to document suppression of arrhythmia. Outpatient follow-up occurred monthly for the first 6 months and every 2nd month thereafter. In three patients it was necessary to administer flecainide every 8 hours because blurring of vision occurred at the time of peak plasma levels when the drug was administered every 12 hours. Flecainide was highly effective in suppressing ventricular arrhythmias when administered twice daily.