Kennedy H L, Sprague M K, Redd R M, Wiens R D, Blum R I, Buckingham T A
Am Heart J. 1986 Apr;111(4):667-72. doi: 10.1016/0002-8703(86)90096-7.
The potential for pharmacokinetic drug interaction between ethmozine (moricizine HCl), a phenothiazine class I antiarrhythmic investigational drug, and digoxin was evaluated in 13 cardiac patients with normal renal function. Antiarrhythmic therapy was initiated in patients with potentially lethal (nonlife-threatening) ventricular arrhythmias (greater than 30 ventricular ectopic beats [VEB]/hr) who were receiving maintenance digoxin therapy for congestive heart failure and/or atrial fibrillation. Serum digoxin concentrations of patients were measured frequently by radioimmunoassay and plasma ethmozine concentrations by high-performance liquid chromatographic methods. Patients entered a short-term (4 weeks) single-blind, placebo controlled ethmozine protocol with an option to receive long-term (1 to 6 months) open-label maintenance ethmozine therapy. Ambulatory ECGs (48 hour) used to assess antiarrhythmic efficacy of ethmozine during each week of the short-term protocol showed that 77% of patients demonstrated greater than 90% mean hourly frequency suppression of all forms of ventricular ectopy. Serum digoxin concentrations during short-term ethmozine dosing showed a nonsignificant (p greater than 0.05) increase of 10% to 15% (mean 0.91 ng/ml to 1.13 ng/ml). The short-term protocol serum digoxin levels correlated closely with serum digoxin concentrations during placebo therapy (1st week, r = 0.90; 2nd week, r = 0.87). Serum digoxin concentrations were not significantly different (p greater than 0.05) from placebo values at the end of 1, 3, and 6 months of maintenance ethmozine therapy. Thus, we conclude that ethmozine administered in an antiarrhythmic efficacious dosage (10 mg/kg/day) showed no important clinical or statistically significant change in serum digoxin concentrations of cardiac patients with normal renal function.
在13名肾功能正常的心脏病患者中，评估了吩噻嗪类I类抗心律失常试验药物乙吗噻嗪（盐酸莫雷西嗪）与地高辛之间药代动力学药物相互作用的可能性。对患有潜在致命性（非危及生命）室性心律失常（每小时大于30次室性早搏[VEB]）且因充血性心力衰竭和/或心房颤动正在接受维持性地高辛治疗的患者开始抗心律失常治疗。通过放射免疫分析法频繁测量患者的血清地高辛浓度，并通过高效液相色谱法测量血浆乙吗噻嗪浓度。患者进入短期（4周）单盲、安慰剂对照的乙吗噻嗪方案，可选择接受长期（1至6个月）开放标签的维持性乙吗噻嗪治疗。在短期方案的每周使用动态心电图（48小时）评估乙吗噻嗪的抗心律失常疗效，结果显示77%的患者所有形式的室性异位心律平均每小时频率抑制超过90%。短期服用乙吗噻嗪期间血清地高辛浓度显示无显著（p大于0.05）升高，升高幅度为10%至15%（平均从0.91 ng/ml升至1.13 ng/ml）。短期方案的血清地高辛水平与安慰剂治疗期间的血清地高辛浓度密切相关（第1周，r = 0.90；第2周，r = 0.87）。在维持性乙吗噻嗪治疗1、3和6个月结束时，血清地高辛浓度与安慰剂值无显著差异（p大于0.05）。因此，我们得出结论，以抗心律失常有效剂量（10 mg/kg/天）给药的乙吗噻嗪在肾功能正常的心脏病患者血清地高辛浓度方面未显示出重要的临床或统计学显著变化。
