Involvement of CYP2C9 alleles in the effectiveness and safety of phenytoin treatment of epilepsy

Current knowledge in Pharmacogenetics allows us to know a genetic polymorphism as a determinant in the response to the administration of numerous drugs, particularly adverse reactions, which bring enormous costs to health systems and risk to people's lives. These variables have a determining influence on the response to drugs and contribute to the determination of the genetic characteristics of people under treatment, which are currently unknown in our population. This will make it possible to establish an important basis for using treatment with an individualized dose for each patient, according to their enzymatic and metabolic profile, with the aim of achieving better control of their condition.
Anticonvulsants such as Phenytoin are commonly used in people with Epilepsy.
The serum concentration of these drugs is commonly adjusted by physicians according to blood levels, but it is known that the therapeutic range when administering these drugs is narrow and adverse reactions, toxicity and even risk of death are frequently observed in people. Phenytoin metabolism is carried out by one of the enzymes encoded by the CYP2C9 cytochrome gene family, whose polymorphisms determine the phenotype of fast metabolizer and slow metabolizer, polymorphisms that have not been studied in our population. In addition, the metabolism of phenytoin is saturable, which puts
particularly high risk for patients with the slow metabolizing phenotype. metabolizing phenotype at particularly high risk. The aim of the present study is to establish whether there is an association between some allelic variants for CYP2C9 genes and the presence of adverse reactions to a drug commonly used in epilepsy.
Adults treated with Phenytoin in monotherapy for the treatment of Epilepsy will be studied, with a sample size of 100 patients (200 alleles). In all of them a venous blood sample (5 mL) will be taken, after informed consent (Annex 1), to proceed to DNA extraction and analysis of the best known alleles for each gene by PCR amplification. Allelic and genotypic frequencies will be established for each gene and it will be determined if they are in Hardy-Weinberg equilibrium. The results will be published in Spanish and English language journals and will serve as the basis for a chapter on pharmacogenetics of antiepileptic drugs in a book to be published by the Iberoamerican Network of Pharmacogenetics and Pharmacogenomics to which the Genetics Unit of the School of Medicine and Health Sciences of the Universidad del Rosario is linked.