1. ¹Department of Pharmacology, Clinical Pharmacology, University of Cologne, Köln, Germany
2. ²Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Ulm, Germany

Correspondence: Dr D Tomalik-Scharte, Department of Pharmacology, Clinical Pharmacology, University of Cologne, Gleueler Strae 24, 50931 Köln, Germany. E-mail:dorota.tomalik-scharte@uk-koeln.de

Received 16 August 2006; Revised 18 April 2007; Accepted 1 May 2007; Published online 5 June 2007.

Abstract

For most drug-metabolizing enzymes (DMEs), the functional consequences of genetic polymorphisms have been examined. Variants leading to reduced or increased enzymatic activity as compared to the wild-type alleles have been identified. This review tries to define potential fields in the therapy of major medical conditions where genotyping (or phenotyping) of genetically polymorphic DMEs might be beneficial for drug safety or therapeutic outcome. The possible application of genotyping is discussed for depression, cardiovascular diseases and thromboembolic disorders, gastric ulcer, malignant diseases and tuberculosis. Some drugs used for relief of these ailments are metabolized with participation of genetically polymorphic DMEs including CYP2D6, CYP2C9, CYP2C19, thiopurine-S-methyltransferase, dihydropyrimidine dehydrogenase, uridine diphosphate glucuronosyltransferase and N-acetyltransferase type 2. Current evidence suggests that taking genetically determined metabolic capacities of DMEs into account has the potential to improve individual risk/benefit relationship. However, more prospective studies with clinical endpoints are needed before the paradigm of 'personalized medicine' based on DME variants can be established.