Research Of Oxcarbazepine Individualized Medication Guided By Patient’s Genotype And Therapeutic Drug Monitoring

Objective By the determination of the serum concentration of active metabolite of oxcarbazepine in serum and HLA-B*1502 genotype of children with epilepsy, the correlation between the serum concentration and daily dose,whether if age, sex or comnination of other drugs have an effect on serum concentration and the gene frequency of HLA-B*1502 which is associated with severe skin reactions induced by oxcarbazepine in the han nationality of xinjiang region were studied to provide the evidence for clinical Individualized medication of oxcarbaezpine.Method 70 Han nationality children who were diagnosed with epilepsy in the department of paediatrics and neurology of our hospital were enrolled and their blood samples were sended to the Institute of clincal medicine.The children were in accord with diagnostic standards of International League Against Epilepsy and they took oxcarbazepine for treatment.Among them, there were 38 children treated with only oxcarbazepine and 32 children treated with oxcarbazepine and other antiepileptic drugs.The fasting blood samples were collected in the morning after oxcarbazepine were took by them at least one week.The blood samples were stord at-80℃ in the refrigerator.(1) To establish a method for the determination of the concentration of monohydroxy-carbazepine in serum by ultra performance liquid chromatography with UV detector,the oxcarbazepine concentration of the serum samples were detected by the method.(2)DNA was extracted from the blood clots.The HLA-B*1502 genotype of the children were tested by the method of PCR-SSP and PCR-SBT.(3)The experimental results and the information of the children were collected to analyze.The measurement data were showed by mean±standard deviation( X ±S).The correlation was analyzed by using linear correlation and linear regression.T-test was used to compare the difference between two group and variance analysis was used to compare the difference among groups.SPSS19.0 software was used to analyze the data. when the P value was less tham 0.05,the difference was considered statistically significant.Results(1)The method established for the determination of the concentration of monohydroxy- carbazepine in serum by ultra performance liquid chromatography is convenient, accurate, sensitive and of good reproducibility. It conforms to the requirements of analysis in biological samples and is suitable for serum concentration monitoring of monohydroxy-carbazepine.(2)When the daily dose of oxcarbazepine of the children was in a range between300 mg to1500mg, the concentration of monohydroxy-carbazepine had a linear correliation with the ratio of dose to weight.the concentration was likely to rise as the ratio increased.Sex or comnination of other drugs had no effect on serum concentration except age.(3)By the method of PCR-SSP and PCR-SBT,there were 3 children who were found HLA-B*1502 gene positive.the gene frequency of HLA-B*1502 of the Han nationality children with epilepsy was 4.29%.Conclusions It is necessary to conduct serum concentration monitoring and HLA-B*1502 gene test for the children with epilepsy who take oxcarbazepine for treatment.It can help doctors evaluate the risk of severe skin adverse reactions and make individualized drug plans for children with epilepsy, thus improve the curative effect of drug, reduce the risk of adverse reactions and improve the patients medication compliance to get epileptic seizure under efficient control.