Disopyramide kinetics in patients with acute myocardial infarction.

The kinetic behavior of disopyramide was studied in 20 patients with suspected myocardial infarction: in 13 of these, the diagnosis was subsequently confirmed. All received a 400-mg oral loading dose of disopyramide base followed by an oral maintenance regimen of either 100 or 200 mg 4 times daily. The elimination half-life (t1/2beta) was longer (p less than 0.05) in patients with confirmed infarction than in patients with unconfirmed infarction [38.0 +/- 3.7 hr (mean +/- SEM) compared to 24.3 +/- 0.8 hr, and 21.2 +/- 2.1 hr compared to 7.2 +/- 2.4 hr for the 100- and 200-mg maintenance dose regimens, respectively]. The t1/2beta was dose dependent for infarct and noninfarct patients. Two of the patients with confirmed infarction failed to reach trough plasma levels equal to or exceeding the lower end of the manufacturer's recommended therapeutic range (3.3 mug/ml) during the study. For the remaining 11 patients the time taken to achieve trough plasma levels of 3.3 mug/ml varied from 18 to 170 hr; hence plasma disopyramide concentration in these patients was suboptimal at a time when the risk of arrhythmias is high. Modification of existing oral loading dose regimens is therefore required for optimization of oral disopyramide therapy.