Analysis Of Efficacy And Influence Factors Of Oxcarbazepine In Paediatric Epilepsy Patients

Objective1.To evaluate the relationship between the dose of oxcarbazepine(OXC)and monohydroxycarbazepine(MHD)serum concentration and clinical efficacy in paediatric epilepsy patients.2.To inverstigate the effect of UGT1A9 I399 C>T,UGT2B7 C.802 T>C and SCN1A IVS5-91 G>A genetic polymorphism on OXC efficacy and the serum MHD concentrations in paediatric epilepsy patients,so as to provide a reference for clinical individualized administration of OXC.Method1.Detection of MHD serum concentration in paediatric epilepsy patients by enzyme enhanced immunoassay(EMIT)method.2.The genotypes of UGT1A9 I399 C>T,UGT2B7 C.802 T>C and SCN1A IVS5-91G>A were detected by Sanger assay.3.The analysis and statistics software is SPSS 22.0.The effect of MHD serum concentration on OXC was analyzed by Pearsonχ~2 test.T test was used to analyze whether there were significant differences in MHD concentrations and other related factors between epileptic seizure group and non-epileptic seizure group.The influence of three genes on MHD concentrations were analyzed by Anova or Fisher’s exact test were used to analyze the effect of three genes on OXC efficacy.Correlation analysis was used to evaluate the correlation between MHD concentrations and OXC dosage.Multivariate regression analysis was used to evaluate the correlation between three genes and MHD concentrations,OXC efficacy.Result1.The linear range of EMIT method to determine the MHD concentration is 1-50μg/mL,the quantitative limit is 1μg/mL,the method recovering is 101.9%~109.8%,the coefficient of variation is less than 10%.2.OXC dose was positively correlated with MHD serum concentration,there are still large individual differences in MHD serum concentration.The mean daily dose of OXC for children with epilepsy was not higher in the effective group[(21.89±6.14)mg/kg/day]than in the ineffective group[(21.93±5.36)mg/kg/day],and the difference between the two groups was not statistically significant(P=0.970).The MHD serum concentration of patients in the epilepsy control group[(14.25±4.84)μg/mL]was significantly higher than that in the epilepsy group[(11.51±4.23)μg/mL](P=0.000).The effective rate of OXC in paediatric epilepsy patients increased when MHD serum concentration of≥16μg/mL(P=0.011),However,there was no significant difference in OXC effective rate when MHD serum concentration of≥17μg/mL(P=0.107).The height and weight of patients in the epilepsy control group were significantly lower than those in the epilepsy group(P<0.05).3.The gene mutation rate of UGT1A9 I399 C>T,UGT2B7 c.802 T>C and SCN1A IVS5-91 G>A were 56.9%,67.1%and 51.0%in 102 paediatric epilepsy patients.UGT1A9 I399 C>T、UGT2B7 802 T>C and SCN1A IVS5-91 G>A gene polymorphism had no effect on MHD serum concentration and OXC efficacy in paediatric epilepsy patients(P>0.05).There was linear correlation between GFR and MHD serum concentration in paediatric epilepsy patients.Conclusion1.MHD serum concentrations determined by EMIT method,high degree of automation,reliable results,stable main technical parameters,meeting the needs of clinical routine monitoring.2.The polymorphisms of genes UGT1A9 I399 C>T,UGT2B7 802 T>C,SCN1A IVS5-91 G>A may be different in different race or region.There was no correlation between UGT1A9 I399 C>T,UGT2B7 802 T>C,SCN1A IVS5-91 G>A and MHD concentrations,OXC efficacy in paediatric epilepsy patients.3.Individual differences in MHD serum concentrations in paediatric epilepsy patients are large,The height and weight of children with epilepsy may be the key factors affecting the dose of OXC.Better clinical outcomes and less adverse reactions may be achieved in paediatric epilepsy patients with an MHD serum concentration between16 and 20μg/mL.