PHARMACOGENETICS OF VALPROIC ACID AS UNMO DIFIED RISK FACTOR OF ADVERSE DRUG REACTIONS

The purpose of the research is the assessment of the role of CYP2C9 gene polymorphisms of the isoenzyme 2С9 of cytochrome Р450 of the liver as unmodified risk factor of adverse drug events development in case of intake of an average therapeutic doses of PA drugs at patients with epilepsy and epileptic syndromes. The studies was carried out within the limits of complex theme of scientific project “Epidemiological, clinical and genetics aspects of diseases of central, peripheral and autonomic neural systems and preventive health care” in 2010-2011. Sampling included 41 cases (patients with epilepsy and epileptic syndromes). Patients were from 1 up to 60 years of age, the median was 23 years. All the carriers of mutant polymorphous allelic variants CYP2C9*2 and CYP2C9*3, both homozygous and heterozygous carriers and also in case of their combination (for example, genotype CYP2C9*2/CYP2C9*3) had 100% occurrence of treatment-emergent adverse events in case of standard usage of VPA drug dosage in accordance with the Pharmacopeia (20-30 mg/kg/per day for children, 20 mg/kg/per day for adults) even during the daily dose titration (10-15 mg/kg/per day for children, 5-10 mg/kg/per day for adults). The homozygous carrier of the gene CYP2C9 of the minor allelic variant of the isoenzyme 2С9 of cytochrome Р450 had the most severe adverse drug reactions in the form of epileptic seizures aggravation, cognitive and behavioral disorders in case of standard usage of VPA drug dosage (kg/ body weight per daily). NATALIA SHNAYDER1,2, MARINA PILUGINA1, DIANA DMITRENKO1, ELENA BOCHANOVA1, EVGENIA SHAPOVALOVA1, SVETLANA ERIKALOVA1, EVGENIA SHMATOVA1, ELVIRA KHAMRAEVA1