The pharmacodynamic and pharmacokinetic differences of the D- and L-isomers of verapamil: implications in the treatment of paroxysmal supraventricular tachycardia

There is increasing interest in defining the pharmacodynamic and pharmacokinetic characteristics of drugs that are marketed as racemic mixtures. Verapamil is one such drug that is commercially available as a mixture of D- and L-isomers. The L-isomer of verapamil has a greater-negative inotropic, negative chronotropic, and negative dromotropic potency than the D-isomer. The values for fraction unbound in serum, distribution volume, and systemic clearance are substantially greater for the L-isomer after intravenous dosing. After oral dosing, the D-isomer achieves peak plasma concentrations five times greater than the L-isomer. The pharmacodynamic and pharmacokinetic characteristics of each isomer are reviewed. The differences in the concentrations of the D- and L-isomers after oral vs intravenous dosing may contribute to the relatively lower efficacy of orally administered verapamil in the treatment of PSVT.