The effect of dextro-, levo-, and racemic verapamil on atrioventricular conduction in humans

Abstract

To study the dromotropic effects of dextro(D)- and levo(L)-verapamil on atrioventricular (AV) conduction in humans, we investigated the prolongation of the PR interval following intravenous administrations of each isomer and racemic preparation (D, 5, 25, and 50 mg; L, 5, 7.5, and 10 mg; racemic, 10 mg). The plasma drug concentration-effect relationship was analyzed by log-linear regression and the sigmoidal Emax model. The sigmoidal Emax model provided a significantly better fit for the data than log-linear regression (p less than 0.01). Maximum drug effect (Emax) and plasma drug concentration associated with 50% Emax (EC50) were calculated by means of the Emax model. The dromotropic potency of each isomer was assessed in terms of EC50 and the drug concentration associated with a 10% PR prolongation from the basal level calculated by the Emax model. The results demonstrated that L-verapamil was 10 and 18 times more potent than D-verapamil in terms of EC50 (D, 188.9 +/- 108.4 ng/ml; L, 17.7 +/- 11.3 ng/ml; p less than 0.05) and drug concentration associated with 10% PR prolongation (D, 166.6 +/- 48.1 ng/ml; L, 9.1 +/- 2.8 ng/ml; p less than 0.01), respectively. A stereospecific difference in plasma protein binding was observed (D, 93.7 +/- 2.2%; L, 88.5 +/- 1.6%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)