5种常用抗癫痫药物的临床使用情况及其血清浓度水平的分析及意义

Clinical application of five commonly used antiepileptic drugs and analysis and significance of their serum concentrations

目的 分析3种新型抗癫痫药物[奥卡西平(Oxcarbazepine, OXC)、左乙拉西坦(Levetiracetam, LEV)及拉莫三嗪(Lamotrigine, LTG)]和2种传统型抗癫痫药物[丙戊酸钠(Valproic acid, VPA)与卡马西平(Carbamazepine, CBZ)]临床使用情况及常规剂量用药后血清浓度水平,为新发癫痫患者进行药物治疗提供依据。方法 回顾性分析2018年1月至2021年12月在安徽中医药大学神经病学研究所附属医院进行抗癫痫药物治疗的1 261例癫痫患者治疗信息。按照用药模式分成4组,分别为单一用药、两药联合、三药联合及四药联合组;按性别分为男性、女性组;按年龄分成6组,分别为≤10岁、11~20岁、21~30岁、31~40岁、41~50岁、≥51岁组。分析并比较各组间的血清药物浓度水平及血药浓度在治疗有效范围的患者例数。结果 癫痫患者单一用药多于联合用药,单一服用OXC最多,联合用药VPA最多。血清药物浓度在有效范围内比率最高的是CBZ、低于有效范围下限最多的是LTG、高于有效范围上限最多的是LEV。单一用药组血清LEV水平[7.87(5.37,9.83)μg/ml]显著高于两药及三药联合用药组[7.05(5.26,9.60)、6.23(4.07,8.94)μg/ml](P<0.05);LTG水平显著低于两药联合组[3.47(1.94,4.73)μg/ml vs.4.37(2.58,7.28)μg/ml,P<0.05],CBZ水平显著高于两药联合组[6.02(4.68,7.48)μg/ml vs.5.25(4.29,6.57)μg/ml,P<0.05]。结论 本研究中,青少年患者首选新型抗癫痫药物、中老年患者首选传统型抗癫痫药物;联合用药首选VPA联合。使用LTG常规剂量进行抗癫痫治疗时,可能需增加剂量;LEV、LTG及CBZ在与其他药物两药联合抗癫痫时需依据血清药物浓度水平及病情对常规使用剂量进行调整。

Objective To analyze the clinical use of three new antiepileptic drugs[oxcarbazepine(OXC),levetiracetam(LEV)and lamotrigine(LTG)]and two traditional antiepileptic drugs[valproic acid(VPA)and carbamazepine(CBZ)],as well as the serum concentration level after conventional dosage,and to provide reference for drug therapy for newly-onset epileptic patients.Methods Retrospective analysis was made on the treatment information of 1261 epileptic patients who were treated with antiepileptic drugs in the Affiliated Hospital of Institute of Neurology,Anhui University of Traditional Chinese Medicine from January 2018 to December 2021.According to the medication pattern,they were divided into four groups:single medication,combination of two drugs,combination of three drugs and combination of four drugs;they were divided into 2 groups according to gender;they were divided into 6 groups according to age:≤10 years old,11~20 years old,21~30 years old,31~40 years old,41~50 years old and≥51 years old.The serum drug concentration level,the number of patients with blood drug concentration in the effective range of treatment were analyzed and compared.Results The number of epilepsy patients in single medication group was more than that in combined medication groups.The top-use drug was OXC in single medication group and VPA in combined medication groups.The highest ratio of serum drug concentration within the effective range was CBZ,the drug most below the lower limit of the effective range was LTG,and the drug most above the upper limit of the effective range was LEV.The serum LEV level of single medication group[7.87(5.37,9.83)μg/ml]was higher than that of combination groups[7.05(5.26,9.60)μg/ml and 6.23(4.07,8.94)μg/ml](P<0.05).The serum LTG level of single medication group was lower than that of combination of two drugs group[3.47(1.94,4.73)μg/ml vs.4.37(2.58,7.28)μg/ml,P<0.05].The serum CBZ level of single medication group was higher than that of combination of two drugs group[6.02(4.68,7.48)μg/ml vs.5.25(4.29,6.57)μg/ml,P<0.05].Serum VPA concentration in male group was higher than that in female group[61.58(44.38,81.72)μg/ml vs.56.67(36.41,73.51)μg/ml,P<0.05].OXC(38.42%)and LEV(40.53%)were used most frequently in the≤10 years group,VPA(52.43%)and CBZ(35.92%)in the 41~50 years group,and LTG(35.91%)in the 21~30 years group.Conclusion In this article,the new antiepileptic drugs are the first choice for adolescent patients,and the traditional antiepileptic drugs are the first choice for middle-aged and elderly patients;VPA combination is the first choice for combined drug use.It may be necessary to increase the dosage of LTG when using conventional dose for antiepileptic treatment.When LEV,LTG and CBZ are combined with other drugs for antiepileptic treatment,the conventional dosage should be adjusted based on serum drug concentration and the condition of patient.