医药导报2016，Vol.35Issue(9)：955-959,5.DOI:10.3870/j.issn.1004-0781.2016.09.011
奥卡西平活性代谢物血清浓度与临床疗效和安全性的关系∗
Relationship Between Serum Concentration of the Active Metabolite and the Efficacy and Safety of Oxcarbazepine
摘要
Abstract
Objective To investigate the relationship between serum 10-hydroxycarbazepine (MHD, the main active metabolite of oxcarbazepine) concentration and oxcarbazepine efficacy and safety, and to optimize rational use of oxcarbazepine. Methods A total of 553 patients were enrolled in a self-controlled and open-label trial to assess the efficacy and safety of oxcarbazepine as monotherapy. The steady state serum MHD trough concentrations after dose were determined by SPE-HPLC. The relationship between MHD level and efficacy were evaluated by logistic regression model and receiver operating characteristic (ROC) curve. Results A total of 498 patients (90.1%) were effective and 404 patients (73.1%) were seizure free after oxcarbazepine monotherapy in this study. The clinical therapeutic range of steady state serum MHD trough concentrations observed in this study was 5 - 20 mg • L-1 , and the corresponding 95% distribution interval of oxcarbazepine daily dose was 9. 0 -34.5 mg•kg-1•d-1 . Logistic regression results indicated a positive correlation of antiepileptic efficacy with serum MHD trough concentration within 0.9-30.0 mg•L-1 . The ROC area (95% confidence interval) of MHD trough concentration as the predictor for efficacy was 0.964 (0.938- 0.990), which showed accurate predictions. Most of patients whould have good antiepileptic efficacy while the steady-state serum MHD trough concentration remains above 8 mg•L-1 . Adverse effects were observed in 104 patients (18.8%) during oxcarbazepine dose escalation phase, and 23 patients (4.2%) during maintenance phase. There were no severe adverse effects associated with oxcarbazepine in this study. Patients with serum MHD concentrations >20 mg•L-1 were at greater risk of developing adverse effects. Conclusion Oxcarbazepine therapeutic efficacy and safety are associated with MHD trough level closely, so it is necessary to monitor MHD concentration.关键词
奥卡西平/10-羟基卡马西平/血药浓度/不良反应Key words
Oxcarbazepine/10-Hydroxycarbazepine/Serum drug concentration/Adverse effect分类
医药卫生引用本文复制引用
汪洋,张华年,陈渝军,徐华,刘茂昌,李思婵,张忠元..奥卡西平活性代谢物血清浓度与临床疗效和安全性的关系∗[J].医药导报,2016,35(9):955-959,5.基金项目
2014年度武汉市临床医学科研项目(WX14C47) （WX14C47）
