Study On The Relation Between Oxcarbazepine Serum Concentration Monitoring And Epilepsy Therapy Efficacy In Children

Objective:1.To investigate the relation between oxcarbazepine(OXC) activemetabolite(10-hydroxycarbazepine,MHD) serum concentration and epilepsy therapy efficacy in children.2.To provide therapeutic range of MHD for Chinese children accepted OXC single-using and drug combination.3.To determine the relationship between MHD serum concentration and OXC dosage(mg/kg.d).4.To investigate the influence of durgs combination and individual difference(sex,age,body weight) on MHD serum concentration.5.To observe the safety of OXC in treatment of children with epilepsy.Methods:By using the method of prospective study, we studied 142 epileptic children accepted OXC (Trileptal, Beijing Novartis, formulation specifications:tablets,150mg or 300mg, suspension,100ml) firstly. These patients were recruited from Children’s Hospital of Chongqing Medical University since July 2013 to November 2014 and information such as sex, age,body weight,dosage,combination with other antiepileptic drugs(AEDs) and so on was recorded in detail.The MHD serum concentration of post-dose samples was measured by high performance liquid chromatography(HPLC).And the related adverse reaction and the clinical curative effect was permanent monitored.Besides,the SPSS 22.0 was used for statistical analysis.Results:1.The efficiency in treatment of epilepsy are 72.0%、75.9%、80.4%、 100.0% in proper order in the four groups(MHD serum concentration less than 3,3-8,8-13,13-17μg/ml),but showing no difference in statistic(P> 0.05). The control group (including complete remission group, remarkably effective group and effective group) of the mean MHD serum concentration (6.62 μg/ml±2.62μg/ml) is significantly higher than the ineffective group (4.84μg/ml±2.13μg/ml),and showing difference in statistic(P=0.000< 0.05).2.The therapeutic range of MHD is (3-12)μg/ml in this study.3.The serum concentration of MHD is correlated with the OXC dose per body weight and there is a linear relationship between serum concentration and dose to weight ratio (R=0.218,P=0.001).4.For the four groups(OXC、OXC+VPA、OXC+LEV、OXC+NZP), there is no difference in 1g C/D(C stands for MHD serum concentration,D stands for OXC dose per body weight) (P>0.05).5.The lgC/D has no difference in different sex,age,body weight(P> 0.05). The 1gC/D in female patients(-0.48±0.22) is higher than male patients(-0.51±0.25). In addition to infant group,the lgC/D has a tendency to increase with sex and age in kiddly group,preschool age group and school age group.6.In this study,35 cases(23.5%) have adverse reactions mainly like rash (4.7%),somnolence (4.7%),headache (3.4%),nausea (3.4%).Most of them are transient,which has no effect on epileptic children’s normal life. MHD average serum concentration of children who arised adverse reactions(7.84μg/ml±2.86μg/ml) is higher than the normal ones (6.03μg/ml±2.54μg/ml),and showing difference in statistic(P=0.000< 0.05).Conclusions:OXC is high safe,and obtains a good clinical efficacy in treatment of children with epilepsy.The MHD serum concentration is closely related to clinical efficacy and OXC dosage.There is a small interaction between OXC and antiepileptic drugs(AEDs),but the individual difference(sex, age, body weight) still has an impact on the serum concentration.So,therapeutic durg monitoring(TDM) is necessary for children.It’s necessary to make individualized remedy according to patients’specific condition and monitoring result in order to achieve maximize effect of antiepileptic OXC.