Kinetics of disopyramide after intravenous infusion to patients with myocardial infarction and heart failure

• Published in: Acta pharmacologica et toxicologica Vol. 56; no. 4; p. 278
• Main Authors: Bonde, J, Angelo, H R, Bødtker, S, Svendsen, T L, Kampmann, J P
• Format: Journal Article
• Language: English
• Published: Denmark 01-04-1985
• Subjects: Aged; Disopyramide - metabolism; Heart Failure - metabolism; Humans; Kinetics; Metabolic Clearance Rate; Middle Aged; Myocardial Infarction - metabolism
• ISSN: 0001-6683
• DOI: 10.1111/j.1600-0773.1985.tb01290.x

Total body clearance, half-life and volume of distribution of disopyramide (Norpace, Searle G.D.) was measured during a six to eight hour infusion to steady state in twenty four patients with either congestive heart failure or acute myocardial infarction and compared to eleven patients without these diseases. All patients were given a bolus injection of 150 mg disopyramide followed by a continuous infusion of 18-24 mg per hour. Serum concentration of disopyramide and its main dealkylated metabolite were determined by HPLC. The clearance in patients without myocardial infarction or congestive heart failure was 1.71 +/- 0.60 ml/min./kg (mean +/- S.D.), not significantly different from those who had either myocardial infarction, congestive heart failure or both. Half-life was 798 min. in patients without heart failure, not significantly different from the values in the other groups. The ratio between disopyramide and its metabolite varied between 3 to 10. Twenty-six % of the steady state serum concentrations of disopyramide were outside the recommended therapeutic range (2-5 micrograms/ml), but no adverse haemodynamic effects were observed in any of the patients. The suggested dosage regimen of disopyramide seems to result in a satisfactory response.