Intravenous quinidine: pharmacokinetic properties and effects on left ventricular performance in humans

Abstract

Ten healthy volunteers received 300 mg. of quinidine base as the gluconate salt by 15-minute intravenous infusion. Physiologic variables monitored before, during, and for 24 hours after the infusion were: electrocardiogram, systolic and diastolic blood pressure, echocardiogram, and carotid pulse tracing. During quinidine infusion, mean ventricular rate increased by 18% (67.1 to 79.5 beats per minute) and corrected QT interval increased by 54% (0.44 to 0.68 sec.). QRS duration did not change significantly, nor did systolic or diastolic blood pressure. Ejection fraction (EF) measured by echocardiography did not decrease during quinidine infusion, but rather increased by 12% (0.58 to 0.65). Mean rate of circumferential fiber shortening (V cf) likewise increased by 22%, from 1.15 to 1.40 per second. Over the 24-hours post-infusion, all monitored physiologic variables fluctuated considerably; in the case of EF and V cf, apparently random variations over time were as great as those attributable to quinidine infusion. Mean (and range) kinetic variables for quinidine were: volume of distribution, 2.03 (1.47 to 3.00) liter/Kg.; elimination half-life, 6.3 (4.8 to 7.9) hours; total clearance, 3.8 (2.8 to 5.2) ml./min./Kg. Neither total nor unbound serum quinidine concentrations were significantly correlated with physiologic changes. Thus, intravenous quinidine in the doses studied did not have negative inotropic effects in a series of healthy humans.