Effect of propranolol on pharmacokinetics and acute electrocardiographic changes following intravenous quinidine in humans.

Abstract

5 healthy volunteers received 4–5 mg/kg of quinidine base by 15-min intravenous infusion on two occasions separated by at least 1 week. Multiple venous blood samples and all urine was collected during the 48 h after each dose and were analyzed for concentrations of total and unbound quinidine (following separation by equilibrium dialysis) by a double-extraction spectrophotofluorometric technique. The first quinidine administration was a ‘control’; for the second quinidine administration, propranolol (40 mg orally every 4–6 h) was given, starting 12 h before the quinidine dosage and continuing for the the duration of the trial. A high degree of β-blockade, assessed by intravenous isoproterenol sensitivity, was achieved by propranolol treatment. Mean (± SE) kinetic variables for quinidine during control and propranolol trials, respectively, were: volume of distribution, 3.0 ± 0.5 versus 2.9 ± 0.5 1/kg (NS); elimination half-life, 7.8 ± 1.1 versus 7.6 ± 0.7 h (NS); total clearance, 4.5 ± 0.6 versus 4.3 ± 0.6 ml/min/kg (NS); renal clearance, 1.58 ± 0.2 versus 1.57 ± 0.2 ml/min/kg (NS); percent unbound, 23.0 ± 1.1 versus 23.6 ± 1.3% (NS). Intravenous quinidine produced tachycardia, T-wave flattening, and prolongation of the QT-interval; none of the changes were influenced by propranolol coadministration. Thus propranolol did not significantly alter the pharmacokinetics or acute electrocardiographic effects of intravenous quinidine in healthy volunteers.