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Norpace, disopyramide phosphate is rapidly and almost completely absorbed, and peak plasma levels are usually attained within 2 hours. The usual therapeutic plasma levels of disopyramide base are 2 to 4 mcg ml, and at these concentrations protein binding varies from 50% to 65%. Because of concentration-dependent protein binding, it is difficult to predict the concentration of the free drug when total drug is measured. The mean plasma half-life of disopyramide in healthy humans is 6.7 hours range of 4 to hours ; . In six patients with impaired renal function creatinine clearance less than 40 ml min ; , disopyramide half-life values were 8 to 18 hours. After the oral administration of 200 mg of disopyramide to 10 cardiac patients with borderline to moderate heart failure, the time to peak serum concentration of 2.3 1.5 hours mean SD ; was increased, and the mean peak serum concentration of 4.8 1.6 mcg ml was higher than in healthy volunteers. After intravenous administration in these same patients, the mean elimination half-life was 9.7 4.2 hours range in healthy volunteers of 4.4 to 7.8 hours ; . In a second study of the oral administration of disopyramide to 7 patients with heart disease, including left ventricular dysfunction, the mean plasma half-life was slightly prolonged to 7.8 1.9 hours range of 5 to 9.5 hours ; . In healthy men, about 50% of a given dose of disopyramide is excreted in the urine as the unchanged drug, about 20% as the mono-N-dealkylated metabolite, and 10% as the other metabolites. The plasma concentration of the major metabolite is approximately one tenth that of disopyramide. Altering the urinary pH in man does not affect the plasma halflife of disopyramide. In a crossover study in healthy subjects, the bioavailability of disopyramide from Norpafe CR capsules was similar to that from the immediate-release capsules. With a single 300-mg oral dose, peak disopyramide plasma concentrations of 3.23 0.75 mcg ml mean SD ; at 2.5 2.3 hours were obtained with two 150-mg immediate-release capsules and 2.22 0.47 mcg ml at 4.9 1.4 hours with two 150mg Nnorpace CR capsules. The elimination half-life of disopyramide was 8.31 1.83 hours with the immediate-release capsules and 11.65 4.72 hours with Norace CR capsules. The amount of disopyramide and mono-N-dealkylated metabolite excreted in the urine in 48 hours was 128 and 48 mg, respectively, with the immediate-release capsules, and 112 and 33 mg, respectively, with Nor0ace CR capsules. The differences in the urinary excretion of either constituent were not statistically significant. Following multiple doses, steady-state plasma levels of between 2 and 4 mcg ml were attained following either 150 mg every-6-hour dosing with immediate-release capsules or 300 mg every-12-hour dosing with Norpace CR capsules. Drug Interactions Effects of other drugs on disopyramide pharmacokinetics: In vitro metabolic studies indicated that disopyramide is metabolized by cytochrome P450 3A4 and that inhibitors of this enzyme may result in elevation of plasma levels of disopyramide. Although specific drug interaction studies have not been done, cases of life-threatening interactions have been reported for disopyramide when given with clarithromycin and erythromycin. Dosage recommendations vary as does the potency of the pills, for example, prednisone.
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