Disopyramide Plasma and Myocardial Tissue Concentrations as They Relate to Antiarrhythmic Activity

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Abstract
Antiarrhythmic concentrations of disopyramide in canine plasma and myocardium were determined by gas chromatography. Ventricular tachycardia was induced in anesthetized dogs by the intravenous administration of ouabain. Disopyramide phosphate was then administered by a two-stage continuous infusion method. A rapid infusion of disopyramide (9.08 mg/kg/hr) was administered for 30 min, followed by a slow infusion (2.18 mg/kg/hr) to maintain steady-state plasma levels of 1.98–2.21, ± SEM = 2.1 ± 0.02/μg/ml at the end of 2 hr. Myocardial tissue levels of disopyramide at steady-state plasma levels were four times those of plasma (atrial tissue, 8.91 ± 0.10; right ventricular free wall, 8.93 ± 0.13; left ventricular free wall, 9.11 ± 0.16/μg/gm wet tissue). The intravenous administration of 80 units crystalline zinc insulin produced both hypokalemia (3.78 ± 0.22 reduced to 2.36 ± 0.18 mEq potassium/liter plasma) and a reappearance of ventricular tachycardia despite no change in plasma and myocardial tissue concentrations of disopyramide from those which had been effective in establishing and maintaining sinus rhythm. The observations demonstrate a relationship between plasma and myocardial disopyramide concentrations such that the former can be used in assessing patient therapy. In addition, this study suggests the importance of plasma potassium in determining the therapeutic effectiveness of disopyramide.

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