基于癫痫患儿治疗药物监测的奥卡西平活性代谢产物血药浓度影响因素分析OACSTPCD
Influencing Factors on Blood Concentration of Active Metabolites of Oxcarbamazepine Based on Therapeutic Drug Monitoring in Children with Epilepsy
目的:探讨癫痫患儿奥卡西平活性代谢产物10-羟基卡马西平(MHD)血药浓度的影响因素.方法:收集2022年8月至2023年8月就诊于我院并规律服用奥卡西平的0～16岁癫痫患儿的血浆样本328例,采用高效液相色谱-质谱法测定奥卡西平活性代谢产物MHD的血药浓度,并分析日剂量和体质量与血药浓度的相关性,探讨年龄、性别、肌酐清除率、尿素和联用抗癫痫药物(AEDs)等因素对MHD血药浓度的影响.结果:通过多元线性回归分析,各因素对MHD血药浓度的影响从大到小依次为日剂量＞体质量＞公斤体质量日剂量＞年龄＞肌酐清除率＞性别＞尿素.MHD血药浓度与日剂量和公斤体质量日剂量呈正相关.婴幼儿的浓度剂量比(CDR)低于儿童和青少年组(P＜0.05).MHD的CDR结果不同性别比较差异无统计学意义(t=1.422,P＞0.05).MHD的CDR与肌酐清除率呈正相关,同时肌酐清除率＞120 mL/min组的CDR高于＜80 mL/min组和80～120 mL/min组(t=-4.539,P＜0.01;t=-5.002,P＜0.01).尿素＜2.9 mmol/L 组的 CDR 大于 2.9～8.2 mmol/L 组(t=2.108,P＜0.05).MHD单药组的CDR高于联用酶抑制AEDs组(U=5 564.00,P＜0.05).结论:临床MHD血药浓度影响因素复杂,个体间药代动力学差异大.日剂量、体质量、年龄、肌酐清除率、尿素和联用酶抑制AEDs是影响MHD血药浓度的重要因素,因此临床应用奥卡西平抗癫痫治疗时应监测癫痫患儿的血药浓度,以期为其提供个体化给药方案支持.
Objective:To explore the influencing factors on blood concentration of active metabolites 10-monohydroxy carbamazepine(MHD)of oxcarbamazepine based on therapeutic drug monitoring in children with epilepsy.Methods:A total of 328 epileptic children aged from 0 to 16 years who regularly took oxcarbazepine were collected from Aug.2022 to Aug.2023.The blood concentration of active metabolites MHD of oxcarbamazepine were determined by high performance liquid chromatography-tandem mass spectrometry.The correlation between daily dose,body mass and blood concentration was analyzed.Effects of age,gender,creatinine clearance rate,urea and combined use of antiepileptic drugs(AEDs)on blood concentration of MHD were investigated.Results:By multiple linear regression analysis,the effects of each factor on blood concentration of MHD were as follows:daily dose＞body mass＞daily per kg dose＞age＞creatinine clearance rate＞gender＞urea.Blood concentration of MHD was positively correlated with daily dose and daily per kg dose.The results of concentration dose ratio(CDR)in infants were significantly lower than those in children and adolescents(P＜0.05).There was no significantly difference in CDR of MHD between different genders(t=1.422,P＞0.05).CDR of MHD was positively correlated with creatinine clearance rate.Meanwhile,the CDR of creatinine clearance rate＞120 mL/min group were significantly higher than those of＜80 mL/min group and from 80 to 120 mL/min group(t=-4.539,P＜0.01;t=-5.002,P＜0.01).The CDR of urea＜2.9 mmol/L group were significantly higher than those from 2.9 to 8.2 mmol/L group(t=2.108,P＜0.05).The CDR of MHD monotherapy group were significantly higher than those of combined enzyme inhibited AEDs group(U=5,564.00,P＜0.05).Conclusion:The factors influencing the blood concentration of MHD are complex and the pharmacokinetics vary greatly among different individuals.Daily dose,body mass,age,creatinine clearance rate,urea and combined enzyme inhibition of AEDs are important factors that affect blood concentration of MHD.Therefore,it is necessary to monitor the blood concentration of oxcarbazepine in clinical antiepileptic treatment to provide individualized medication regimen support.
马英华;安娜;安志华;赵宜乐
河北省儿童医院,石家庄 050031
药学
奥卡西平10-羟基卡马西平血药浓度影响因素儿童
oxcarbazepine10-monohydroxy carbamazepineblood concentrationinfluencing factorschildren
《儿科药学杂志》 2024 (008)
1-5 / 5
河北省卫生健康委员会2021年度医学科学研究课题计划项目,编号20211469.
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