4种新型抗癫痫药物治疗新疆癫痫患儿的疗效评估及血药浓度参考范围的建立

Evaluation of the clinical efficacy, safety, and establishment of reference ranges for plasma concentrations of four new antiseizure medications in the treatment of children with epilepsy in Xinjiang

关键词:  拉考沙胺  左乙拉西坦  奥卡西平  拉莫三嗪  血药浓度

Key words:  lacosamide  levetiracetam  oxcarbazepine  lamotrigine  plasma concentration

摘要:

目的 通过分析拉考沙胺（lacosamide，LCM）、左乙拉西坦（levetiracetam，LEV）、奥卡西平（oxcarbazepine，OXC）和拉莫三嗪（lamotrigine，LTG）血药浓度、疗效和安全性间的相关性，并建立其有效血药浓度参考范围。 方法 收集722、1055、1215、680例服用LCM、LEV、OXC和LTG的癫痫患儿的血液样本。采用超高效液相色谱法测定其血浆药物浓度，分析4种抗癫痫药物给药剂量与血药浓度的相关性，同时探讨其治疗癫痫患儿临床疗效的影响因素，并建立癫痫患儿的LCM、LEV、OXC和LTG稳态血药浓度参考区间。 结果 LCM、LEV、OXC和LTG治疗有效率分别为77.7%、82.7%、76.7%和76.6%；不良反应发生率分别为34.8%、33.5%、25.7%和32.1%。OXC和LTG给药剂量与血药浓度的相关性较好（r > 0.6），LCM和LEV给药剂量与血药浓度的相关性均较差（r < 0.5）。LCM、LEV、OXC和LTG血药浓度对于疗效的预判准确性 [AUC(95%CI) = 0.535、0.579、0.526和0.617]均高于给药剂量[AUC(95%CI) = 0.484、0.488、0.477和0.483]。癫痫患儿的LCM、LEV、OXC和LTG血药浓度参考范围分别为：2.0～15.0 μg·mL-1、8.2～24.2 μg·mL-1、9.8～31.9 μg·mL-1和2.1～15.2 μg·mL-1。 结论 临床有必要定期监测癫痫患儿的LCM、LEV、OXC和LTG血浆浓度，以确保其控制在治疗范围内，以便于及时调整给药剂量，预防药物蓄积过量而减少不良反应发生率。

Abstract:

OBJECTIVE This study aims to analyze the correlation between the plasma concentrations, efficacy, and safety of lacosamide (LCM), levetiracetam (LEV), oxcarbazepine (OXC), and lamotrigine (LTG), and to establish a reference range for their effective plasma concentrations. METHODS Blood samples were collected from 722, 1055, 1215, and 680 pediatric epilepsy patients taking LCM, LEV, OXC, and LTG, respectively. This study used ultra-high performance liquid chromatography to determined plasma concentrations and analyzed the correlation between the dosages and plasma concentrations of LCM, LEV, OXC, and LTG. At the same time, this study explored the factors affecting the efficacy of LCM, LEV, OXC, and LTG in children with epilepsy, and established the reference ranges for their plasma concentrations. RESULTS The efficacy rates of LCM, LEV, OXC, and LTG were 77.7%, 82.7%, 76.7%, and 76.6% respectively. The incidence rates of adverse reactions were 34.8%, 33.5%, 25.7%, and 32.1% respectively. The correlation between the dosing of OXC and LTG with plasma concentration was good (r > 0.6), while the correlation for LCM and LEV was poor (r < 0.5). The predictive accuracy of LCM, LEV, OXC, and LTG plasma concentrations [AUC(95%CI) = 0.535, 0.579, 0.526, and 0.617] for efficacy in children with epilepsy was higher than that for dose [AUC(95%CI) = 0.484, 0.488, 0.477, and 0.483]. The reference ranges for steady-state plasma concentrations of LCM, LEV, OXC, and LTG in children with epilepsy were 2.0 to 15.0 μg·mL-1, 8.2 to 124.2 μg·mL-1, 9.8 to 31.9 μg·mL-1, and 2.1 to 15.2 μg·mL-1, respectively. CONCLUSION It is necessary to regularly monitor the plasma concentrations of LCM, LEV, OXC, and LTG in children with epilepsy in a clinical setting to ensure they are maintained within the therapeutic range, facilitating timely adjustments in medication dosage to prevent drug accumulation and reduce the incidence of adverse reactions.