Yevhen Tantsura V.N.
Karazin Kharkiv National University, Department of General practice-Family Medicine, Kharkiv
Title: The frequency of isoenzymes of cytochrome P450 – СУР3Ð4 in children with drug-resistant epilepsy in Ukraine
Submitted Date: 27-09-2018
Biography
Yevhen Tantsura is currently working as an assistant of the Department of General practice Family Medicine of the V. N. Karazin’s Kharkiv National University,Kharkiv, Ukraine
Abstract
Objective: The frequency with which drug-resistant epilepsies occur is unchanged and reaches 30-40%. It is believed that isoenzymes of cytochrome P450 can significantly affect the metabolism, efficacy and safety of AEDs.rnThe purpose of our study was to: find out in children with pharmaco-resistant epilepsy the frequency with which polymorphism of isoenzymes of cytochrome P450 – CYP3Ð4 occurs taking part in biotransformation of most AEDs.rnMaterials and methods: We analyzed the results of an examination of 68 patients (children and adolescents), 42 (62.69%) boys and 26 (37.31%) girls, aged from 5 months to 18 years, the average age was 9.6 ± 5.65 years. Children suffer from severe, refractory to the treatment forms of epilepsy. Duration of the disease from 1 month to 16 years. All children were given genetic research using the allelic method of a specific PCR with the subsequent visualization of the products of amplification in agarose gel. We determined the frequency with which the genotypes CYP3A4 * 1A, * 1B were found.rn Research results: Before us nobody has conducted such kind of studies in Ukraine. In the study group allele CYP3A4*1A dominated in 61 patient (89,71%). This genotype is quite common in many populations and is typical for fast metabolizers. The carrier of CYP3Ð4*1Ð’ allele, which is functionally linked with biotransformation of drugs, slowing down their metabolism, was found in 7 (10,29 %) of patients. In 4 (57.13%) of them were reported undesirable side effects at different stages of the disease and consequently of antiepileptic treatment. Adverse pharmacological responses were in the form of allergic reactions and disorders from the nervous system. This result coincides with the results of population surveys among Caucasians - where the frequency of the allelic variant of CYP3A4 * 1B - is 9%. At the same time, pharmacological studies by Indian experts conducted with the determination of the frequency of the genetic polymorphism of CYP3A4 * 1V in 23 children with pharmacoresistant epilepsy and in 7 children with good-cured epilepsy showed a significant difference (78.3% in drug-resistant epilepsy and 14.3% in control patients). The results demonstrated the important role of the CYP 3A4*1B allelic variant as risk factor for developing of drug resistance. rnConclusions: The carrier of allele variant CYP3Ð4*1Ð’ among children with refractory to the treatment epilepsy in 10,29%. Often, these children experienced undesirable side effects – in 57.13% of cases, from the nervous system and allergic manifestations.rn