Anca Dana Buzoianu 1, Corina Ioana Bocşan 1, Claudia Militaru 1
1 Department of Clinical Pharmacology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Abstract
Pharmacogenomics developed mainly in the past 10 years, at the same time with the sequencing of the human genome and the introduction of the new technologies that made possible the analysis of more than one gene at the same time. Pharmacogenomics investigates the way that the variations of the human genome influence the specific responses to the medicines and allows the adaptation of the medication to the individual genetic constellation of a person, through “patient tailored” treatments, with increased efficacy and safety. The polymorphism of the genes that are involved in the metabolism of anti-epileptic drugs determine modified activity of the encoded enzymes; consequentially, differences result regarding the plasmatic concentration of the drugs, and there are also differences in the therapeutic efficacy and safety, more evident in the case of medicines with narrow therapeutic window. Genotyping CYP2C19 and CYP2C9 represents an alternative for traditional methods of investigation of the phenotype, and a predictive method for the low metabolizer status of the individual, status related to the increase of drugs’ toxicity and to more frequent side effects. Acenocoumarol is the main drug used for the prophylaxis and treatment of thromboembolic disease (TED) in Romania, although its adverse effects are causing 10% of the hospitalizations in the U.S.A. and Europe. There is a high inter-individual variability of the CYP2C9, with implications in the metabolism of acenocoumarol. Variability is caused mainly by the two frequent polymorphisms of the gene CYP2C9, CYP2C92 and CYP2C93. Patients carrying this polymorphism, G-1639A, can have an increased hemorrhagic risk, even with medium doses of acenocoumarol. Therefore, genotypic analysis seems to be a promising clinical approach for reducing the adverse effects of drugs and for increasing their efficacy, being an actual preoccupation of many research teams worldwide.