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BACKGROUND Epilepsy is a chronic neurological disease characterized by recurrent unprovoked seizures. Therapeutic drug monitoring (TDM) has often been performed during the pharmacological treatment of epilepsy, but the plasma levels of some AEDs do not correlate well with the doses and/or the therapeutic or toxic effects of the drugs. OBJECTIVE Objective of the study is to evaluate the pattern of polymorphism in UGT1A3 in pediatric epileptics on valproate. It also aims to find the association between gene polymorphism and plasma concentration of valproate, its clinical effectiveness and its adverse effect profile. METHODS One hundred children aged 2-18 years with a diagnosis of epilepsy and treated with sodium valproate mono therapy will be included in the study. Their demographic profile, type of seizure, dose and frequency of sodium valproate will be recorded. Five ml of venous blood will be collected after 30 days of starting the regimen,3ml EDTA blood will be utilized for genotyping by PCR-RFLP method and for platelet count, 2 ml plain blood will be used for estimating serum drug concentration by HPLC and for biochemical tests. The patient will be followed up quarterly or more frequently (as deemed by the clinician) for clinical evaluation. Statistical analysis: Hardy-Weinberg equilibrium (HWE) analysis will be performed on UGT1A3 polymorphisms. ANOVA will be used to investigate the association between genotypes distribution and serum concentration of VPA. A p-value RESULTS The study is funded by Indian council of Medical research, sanction letter dated 19.08.2019 No.5/4-5/187/Neuro/2019-NCD-I. The university ethical approval was obtained, ref NU/CEC/2019/0223.A total of thirty samples are collected at the end of six months.PCR-RFLP and HPLC methods are standardized and results will be available on completion of the study. CONCLUSIONS Genetic polymorphisms of UGTs may influence VPA metabolism and hence the steady-state concentration of the drug in plasma may be altered. This may demand an increased or reduced dose of VPA in epileptics so as to maintain the therapeutic levels. The study may be useful in optimizing the anti-epileptic dosage. CLINICALTRIAL NOt applicable. |
