摘要
目的：探讨左乙拉西坦（LEV）单药治疗时的血药浓度水平与其临床疗效的关系,以促进合理用药。方法：对245例5个月～16岁口服左乙拉西坦单药治疗的癫痫患儿进行开放性自身对照随访研究,观察疗效和不良反应。采用固相萃取-高效液相色谱法（SPE-HPLC）测定患儿血样中LEV的稳态谷浓度,运用受试者操作特征（ROC）曲线分析该浓度水平与疗效的关系。结果：左乙拉西坦单药治疗本组癫痫患儿的有效率为88.6%（217例）,其中完全控制率为66.1%（162例）。对于本组患儿临床有效的LEV稳态谷浓度参考范围为5～19 mg·L^-1,相应的LEV日剂量的95%分布区间为13.9～50.0mg·kg^-1·d^-1。以谷浓度作为疗效预测因子构建的ROC曲线下面积AUC（95%CI）=0.925（0.884～0.967）,显示出较高的预测准确性。Youden指数最大（0.717）时对应的ROC曲线上最佳界值切点为6.05 mg·L^-1,说明当LEV稳态谷浓度超过6 mg·L^-1时大多病例会获得满意疗效。本组研究中左乙拉西坦的不良反应发生率在初始加量阶段为14.3%（35例）,剂量稳定后自然消除,未发现严重不良反应。结论：左乙拉西坦的临床疗效和其谷浓度水平密切相关,为保证疗效和安全性,有必要监测血药浓度。
OBJECTIVE To investigate relationship between serum concentration and clinical efficacy of levetiracetam（LEV）monotherapy,and optimize rational use of LEV.METHODS A self-controlled and open-label trial had been performed in245 epileptic children aged from5 months to 16 years,and treated with LEV monotherapy,to assess efficacy and safety of LEV.Steady state trough concentrations of serum LEV of children were determined by solid phase extraction and high performance liquid chromatography（SPE-HPLC）.A receiver operating characteristic（ROC）curve was used to analyze the relationship between serum levels and efficacy of LEV.RESULTS A total of 217 patients（88.6%）had more than50%reduction of seizure frequency,162（66.1%）patients became seizure-free after treated with LEV monotherapy in this study.Clinical therapeutic range was 5-19 mg·L^-1 for steady state trough concentrations of serum LEV observed in this study,and corresponding 95%distribution interval of LEV daily dose was 13.9-50.0mg·kg^-1·d^-1.Area under ROC（AUC）of LEV trough concentration as predictor for efficacy was 0.925[95%confidence interval（CI）,0.884-0.967],which showed highly accurate predictions.When Youden index was the largest（0.717）,the best threshold of response was 6.05 mg·L^-1,which indicated that most patients would have good antiepileptic effects when steady state trough concentration of serum LEV was above 6 mg·L^-1.In this study,adverse effects were observed in35 patients（14.3%）during LEV dose escalation phase,and spontaneously disappeared during dose steady phase.No severe adverse reaction occurred.CONCLUSION Therapeutic efficacy of LEV is associated with its trough serum levels closely,and it is necessary to monitor LEV concentrations for improving efficacy and safety.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2016年第6期476-480,共5页
Chinese Journal of Hospital Pharmacy
关键词
左乙拉西坦
血药浓度
临床疗效
儿童
levetiracetam
serum concentration
clinical efficacy
children
