Prophylactic Disopyramide: Its Clinical Effects Related to Plasma Concentration in Myocardial Infarction

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Abstract
Sixty-three patients, fifty-two with acute myocardial infarction and eleven with ischaemic heart disease or non-cardiac chest pain, were given either disopyramide phosphate or placebo, orally, in a randomized double-blind study. Thirty-two patients on disopyramide (twenty-six with acute myocardial infarction) received an initial dose of 300 mg followed by 150 mg six-hourly for 3 days. There was a reduction in the number of patients with cardiac dysrhythmias on the first 3 days following infarction in subjects taking disopyramide as compared with controls. This reduction was not statistically significant. There was a significant reduction in the mean ectopic count per hour in patients taking disopyramide compared with those taking placebo on the second day only (p < 0.005). Urinary retention, dry mouth and jaundice were recorded more frequently in the test group. There were wide ranges of pre-dose plasma concentrations on all 3 days. (Day 1: 1.3 to 7.7 μg per ml. Day 2: 2.5 to 8.9 μg/ml and Day 3: 2.5 to 11.5 μg per ml). The mean plasma concentration of disopyramide was higher but not significantly so, in the treatment group without evidence of dysrhythmias than those with dysrhythmias (3.8 ± S.D. 1.5 μg/ml and 3.0 ± 0.8 μg/ml respectively). The mean plasma level in patients who required anti-emetic therapy was significantly lower than those who did not (2.8 ± 0.8 μg/ml and 3.8 ± 1.9 μg/ml respectively, p < 0.025). The wide range of plasma levels observed is probably due in part to irregular absorption with vomiting after myocardial infarction. If disopyramide is to be used prophylactically following myocardial infarction, a therapeutic plasma level will be achieved quickly in all cases only by giving an intravenous starting dose.