by icia icia

Objectives:
the elaboration of a personalized treatment scheme, in the antiepileptic treatment, a scheme that will take notice of the individual farmacogenomic parameters.

OBJECTIVES
  • the elaboration of a personalized treatment scheme, in the antiepileptic treatment, a scheme that will take notice of the individual farmacogenomic parameters.
DESCRIPTION In the production of the multidrug resistance it seems like the glycoprotein’s (p-170) gene is involved (ABCB1) known under the name MDR1, whose raised expression seems to influence the response to antiepileptic treatment. In the current study we intent to investigate the connection between the polymorphisms of the genes CYP2C9, CYP2C19 and the individual metabolic status of patients and between the polymorphisms of the MDR1 gene and the multi-drug resistance to the antiepileptic treatment. Patients with idiopathic epilepsy will be studied, and completely evaluated at the beginning of the study, clinic, imagistic, electric, psychiatric and cognitive, in order to exclude the secondary forms of epilepsy and the convulsive crises of any other nature. The study will be realized according to the ethic standards in concern with the Declaration from Helsinki and the Romanian legislation in cause. A treatment adequate to the disease form will be prescribed to each patient, in monotherapy or polytherapy and their evolution will be observed for one year, concerning the clinical evolution of the disease under the prescribed therapy. After a year from the beginning of the study, the patients will be evaluated again clinically, electrical, and cognitive by neuropsychological assessment. According to the clinical evaluation the patients will be divided into two categories: responders and non-responders. The hypothetical connection between the expression of the MDR1 gene and the refractory form of the disease will be explored by comparing the frequencies of the obtained alleles and the analysis of the logistic regression using specific statistic programs for genetic studies. The next phase contains the phenotypic study of the metabolic status of the patients by the determination of the plasmatic concentrations of the medicine used in therapy and the main pharmacokinetic parameters, which will be analyzed and correlated to the results obtained after genotype determination, resulting a correlation
between genic polymorphism and phenotypic pharmacokinetic parameters (genotype-phenotype correlation). The possible relations between the obtained results after genotype determination and the toxicity of the drugs will be evaluated, the possibility of the side reactions and toxic plasmatic concentrations to be the result of the slow metabolizing status of the patients, due to some polymorphisms of the CYP2C9 and CYP2C19 genes.
RESULTS ESTIMATED
  • a pharmacogenomic study laboratory will be created that could serve several medical units, laboratory that can obtain ulterior finance and result in the growth of the medical performances, with favourable economical involvements;
  • scheme based on the pharmacogenomic mapping, as well as the determination of the drugs pharmacokinetics which will allow to choose the treatment in the adequate dose, for the existing enzymatic status;
  • the correlation degree of between the genes polymorphisms and drugs kinetics;
  • individualized treatment schemes in function of the obtained farmacogenomic parameters.
RESULTS OBTAINED
Other Informations
Attached documents: