The impact of genetic polymorphism of cytochrome p-450 2C9 and 1A2 isoforms on warfarine metabolism

Abstract

The influence of genetic polymorphism on the scope of drug metabolism is now well-known, since the metabolism of drugs depends on the amount of active enzyme in human tissues, primarily in the liver. The aim of the paper is to process data related to genetic polymorphism of isoforms of cytochrome enzymes that are important for metabolism and dosing of warfarin, considering that serious adverse effects can sometimes end with a fatal outcome. In addition, the systemic review article pointed to the importance of pharmacogenomic studies prior to the introduction of warfarin in therapy. A systematic research of literature using the medical databases 'Pub Med' and ‘Google Scholar’ found a total of 251 publications. The results included eight publications that met the criteria for inclusion. The extraction of the most important data from all works necessary for an adequate evaluation was performed and presented in seven tables containing general data of studies and pharmacokinetic parameters related to the metabolism of warfarin. The therapeutic effect of coumarin derivatives such as warfarin is influenced by genetic factors, but also other factors related to the patient. The frequent mutations of the gene encoding the cytochrome P450 isoform CYP2C9, but also the vitamin K-epoxide reductase with one or more polymorphic combinations, are responsible for reducing the required dose of warfarin or even for resistance to warfarin. Although genotyping data improves the accuracy of dose prediction, the improvement in controlling the anticoagulant effect and warfarin metabolism has yet to be proven in terms of effectiveness and cost-effectiveness in future prospective clinical studies.