Purpose : Decrease of frequency and weight of the side effects
at therapy by valproic acide in mono and polytherapies in
patients with epilepsy.
Method : We examined 113 patients aged from 4 up to 57 years
with epilepsy accepting valproic acide in monotherapy
of 35.8% or polytherapy — 64.2% (Carbamazepin or
topiramate). Average age of patients was 27 years, 49 men
(43.4%) and 64 women (56.6%). The genetic form of epilepsy
was diagnosed for 55 patients (49%), at 55 patients (49%)
structural epilepsy, is diagnosed for 3 patients (2%) - not
specified. Using of the PCR- RFLP analysis polymorphisms
in genes of valproic acid metabolism were studied in patients
with epilepsy and in North- Western region population of
Russian Federation: P- glycoprotein — MDR1 ( 3435C > T ),
cytochromes P450 — CYP2C9 ( 430C > T
1075A > C ) and CYP2C19 (681G > A) . Assessment of
dynamics of undesirable side effects was made objective
and on the basis of complaints of patients in the course of
the research at repeated visits to the attending physician, the
reduced Naranzho′s scale was used (the question of placebo
was excluded from poll).
Results : As compared with unaffected patients, in people
with chronic adverse events statistically significant
increase of «mutant» allele in gene CYP2C9 (1075A > C)
was identified (3.5% and 14.5%, respectively, F < 0.03).
The interrelation between a pharmakorezistent at treatment
of patients with epilepsy and a polymorphism of genes
of P- 450 cytochromes ( CYP2C9, CYP2C19 ) and MDR1
wasn′t revealed.
Conclusion : The prospects of pharmacogenetic testing at
epilepsy consist in creation of set of gaplotip for initial
determination of risk of development of the undesirable
phenomena against the background of therapy by various
medicines that in the future will allow the personalized
medicine to take the central place in clinical practice.
Application of pharmacogenetic testing can raise a
treatment compliance.