Racemic mixtures: harmless or potentially toxic?

Abstract

Issues involved in the development and evaluation of racemic drug mixtures are described. Administration of a racemic drug mixture is in reality administration of two drugs with distinct pharmacokinetic and pharmacodynamic properties. Compared with the active enantiomer, the inactive enantiomer in a racemic mixture often has different rates of absorption, metabolism, and excretion, as well as different affinities for tissue receptor and protein receptor binding sites. It may be an agonist or antagonist, produce adverse effects, increase efficacy, or place an undue burden on clearance mechanisms. Thus, the pharmacokinetic and pharmacodynamic properties, pharmacologic activity, and toxicity of each enantiomer in a racemic drug mixture need to be determined. When pharmacokinetics of enantiomers differ, the contribution of each enantiomer to effectiveness and toxicity and whether the mixture may be more beneficial than a single enantiomer will need to be considered before racemic mixtures are marketed.