丙戊酸单药治疗癫痫患儿导致肉碱缺乏的危险因素研究  

Risk factors for carnitine deficiency associated with valproic acid monotherapy in epileptic children

作　　者：马艺溢 陈亚南[1] 赵明明[1] 肇丽梅[1] MA Yi-yi;CHEN Ya-nan;ZHAO Ming-ming;ZHAO Li-mei(Department of Pharmacy,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院药学部,沈阳110004

出　　处：《中国临床药理学杂志》2018年第24期2811-2813,共3页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81673510)

摘　　要：目的探讨接受丙戊酸(VPA)单药治疗的儿童游离肉碱和酰基肉碱水平的变化以及丙戊酸导致肉碱缺乏危险因素。方法检测99例单用丙戊酸治疗2个月以上、年龄≤16岁的癫痫患儿(试验组)及50例健康儿童(对照组)的游离肉碱及酰基肉碱水平,用Mann-Whitney U检验分析肉碱水平的变化。通过多因素Logistic回归分析患儿性别、年龄、丙戊酸日剂量、服药时长、丙戊酸浓度、血氨等因素对丙戊酸导致肉碱缺乏的影响。结果试验组游离肉碱和总肉碱水平[27. 13(11. 59),37. 07(14. 16)μmol·L^(-1)]显著低于对照组[35. 08(12. 98),49. 88(18. 70)μmol·L^(-1)](P <0. 01),总酰基肉碱及短链(C2-C5)酰基肉碱水平较对照组明显下降(P <0. 01),中链(C6-C12)和长链(C14-C18)酰基肉碱与对照组相比差异无统计学意义,但二者与游离肉碱的比值均升高(P <0. 01)。18例(18. 2%)单用丙戊酸的癫痫患儿出现了肉碱缺乏,其中16例患儿无症状。高血氨(P <0. 05)和高丙戊酸浓度是丙戊酸导致肉碱缺乏的危险因素(P <0. 05)。结论单用丙戊酸可导致游离肉碱和酰基肉碱水平下降。高血氨和高丙戊酸浓度患儿更易出现肉碱缺乏。对于高危患者应筛查游离肉碱和酰基肉碱,及时诊断并进行治疗。Objective To explore the changes of free carnitine and acylcarnitine levels in children receiving valproic acid VPA) monotherapy and the risk factors for carnitine deficiency associated with VPA. Methods The levels of free carnitine and acylcarnitine in 99 children aged≤16 years) with epilepsy receiving VPA monotherapy and those in 50 healthy children control group) were analyzed. Mann-Whitney U test was used to analyze the levels of carnitine. Multivariate Logistic regression was used to evaluate the relevant factors,such as gender,age, VPA daily dosage,duration of treatment,plasma VPA levels,and plasma ammonia tocarnitine deficiency associated with VPA. Results The levels of free carnitine and total carnitine in treatment group [27. 13 11. 59) ,37. 07 14. 16) μmol·L ^- 1] were significantly lower than those in control group[35. 08 12. 98) ,49. 88 18. 70) μmol·L^-1] P < 0. 01) . Acylcarnitine and short-chain C2-C5) acylcarnitine levels decreased significantly compared with control group P < 0. 01) . Medium chain C6-Cl2) and long-chain C14-C18) acylcarnitine levels were no statistically different in two groups,but the ratio of medium chainand long-chain acylcarnitine to free carnitine increased P < 0. 01) . Carnitine deficiency occurred in 18 18. 2%) epileptic children on VPA monotherapy, and 16 children were asymptomatic. High plasma ammonia P < 0. 05 ) and high plasma VPA concentrations P < 0. 05) were risk factors for carnitine deficiency associated with VPA. Conclusion VPA mono-therapy can result in decreased levels of free carnitine and acylcarnitine. Carnitine deficiency is more likely in children with high plasma ammonia and high plasma VPA concentrations. Therefore,for high-risk patients,free carnitine and acylcarnitine should be screened and diagnosis and treatment of carnitine deficiency without delay might be useful for patients.

关 键 词：肉碱缺乏 丙戊酸 酰基肉碱 危险因素 

分 类 号：R97[医药卫生—药品]