Pharmacodynamics of the antiarrhythmic disopyramide in healthy humans: Correlation of the kinetics of the drug and its effects

Abstract

The effects on heart rate, R-T' interval, and mean arterial blood pressure were studied in seven healthy male volunteers after intravenous (1 and 2 mg/kg) and oral (3 and 6 mg/kg) administration of the quinidine-like antiarrhythmic disopyramide phosphate, 4-diisopropylamino-2-phenyl-2-(2-pyridyl)butyramide phosphate. The left ventricular ejection time was measured after intravenous administration of 2 mg/kg of drug. Simultaneously the plasma concentrations and urinary excretion of the parent drug and its main metabolite, the monodealkylated product, were monitored as a function of time. Heart rate increases of 20% were observed at 2 mg/kg i.v. and 6 mg/kg p.o. and peaked at 0–4 min and 2 hr after administration, respectively. R-T' interval increases of 40% and 9% were observed at 2 mg/kg and 1 mg/kg i.v., respectively, and peaked at 0–2 min after administration. R-T' interval increases of 12% and 4% were observed at 6 mg/kg and 3 mg/kg p.o., respectively, and peaked at 2.5 hr. The ejection time index was unchanged, and although a 5–10% increase in the mean arterial blood pressure was observed in the 11 hr after administration, there was no pattern consistent with size or mode of administration of the four different dosages.