Nauta I L, van de Calseyde J, Hertzberger D P
Curr Med Res Opin. 1983;8(8):582-93. doi: 10.1185/03007998309109802.
A study was carried out in 33 patients with myocardial infarction and complicating arrhythmias to compare plasma levels of disopyramide attained after administration of conventional capsules or sustained-release tablets. On Day 1, 29 patients started treatment wtih 600 mg disopyramide in 3 divided doses of conventional capsules. In 18, disopyramide plasma concentrations of 3 mg/l or more were achieved within 300 minutes after the first dose. On the second day, patients were allocated at random to receive treatment double-blind for 11 days with 500 mg disopyramide daily given either as conventional capsules (17 patients) or as sustained-release tablets (16 patients). Plasma concentrations were measured just before and 3 hours after the morning dose. Mean maximum and minimum concentrations in the conventional capsule group were 4.4 mg/l and 2.8 mg/l, respectively, compared to 4.3 mg/l and 3.0 mg/l, respectively, in the sustained-release tablet group. For the next 30 days all patients continued treatment with sustained-release tablets. Mean disopyramide plasma concentration measured 15 to 18 hours after the last dose was 2.8 mg/l. Myocardial function was estimated during and 1 week after discontinuing disopyramide treatment. The mean fractional fibre shortening (echocardiography) during treatment was 23% less than that 1 week after discontinuation. The mean PEP/LVET (systolic time interval recording) was 7% higher during treatment compared with 1 week after discontinuation. In 4 cases, mean ejection fraction, measured by scintigraphic methods, during treatment was 10% less than 1 week after discontinuation. Anti-arrhythmic effect was investigated by continuous monitoring in the first 12 days and by Holter monitoring during the 30-day ambulant period and 1 week after discontinuing disopyramide. A significant reappearance of warning arrhythmias could be detected after discontinuing disopyramide sustained-release tablets. No anti-arrhythmic effect was detected in 4 patients. Six patients had to be withdrawn because of side-effects. It is concluded that disopyramide sustained-release tablets 500 mg per day in 2 divided doses gives therapeutic plasma concentrations of 3 mg/l comparable with conventional capsules. A myocardial depressive effect is noted of about 10%.
对33例心肌梗死并发心律失常患者进行了一项研究，以比较服用常规胶囊或缓释片后所达到的丙吡胺血浆水平。第1天，29例患者开始用600mg丙吡胺，分3次服用常规胶囊。18例患者在首剂后300分钟内丙吡胺血浆浓度达到3mg/l或更高。第2天，患者被随机分配，双盲接受为期11天的治疗，每天服用500mg丙吡胺，分别给予常规胶囊（17例患者）或缓释片（16例患者）。在晨服前和服药后3小时测量血浆浓度。常规胶囊组的平均最大和最小浓度分别为4.4mg/l和2.8mg/l，而缓释片组分别为4.3mg/l和3.0mg/l。在接下来的30天里，所有患者继续用缓释片治疗。末次给药后15至18小时测得的丙吡胺平均血浆浓度为2.8mg/l。在停用丙吡胺治疗期间及停药1周后评估心肌功能。治疗期间的平均心肌纤维缩短分数（超声心动图）比停药1周后低23%。与停药1周后相比，治疗期间的平均PEP/LVET（收缩期时间间期记录）高7%。4例患者中，通过闪烁扫描法测得的治疗期间平均射血分数比停药1周后低10%。在开始的12天内通过连续监测以及在30天门诊期和停用丙吡胺1周后通过动态心电图监测来研究抗心律失常作用。停用丙吡胺缓释片后可检测到有明显的警示性心律失常再次出现。4例患者未检测到抗心律失常作用。6例患者因副作用而停药。得出的结论是，每天2次服用500mg丙吡胺缓释片可产生与常规胶囊相当的3mg/l治疗性血浆浓度。观察到约10%的心肌抑制作用。
