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引用本文:段亦非,李宛凌,赖婉琳,陈蕾.女性癫痫患者妊娠期抗癫痫药物药动学变化及应对措施[J].中国现代应用药学,2022,39(15):2039-2044.
DUAN Yifei,LI Wanling,LAI Wanlin,CHEN Lei.Pharmacokinetic Changes of Antiseizure Medications and Coping Strategy During Pregnancy[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(15):2039-2044.
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女性癫痫患者妊娠期抗癫痫药物药动学变化及应对措施
段亦非, 李宛凌, 赖婉琳, 陈蕾
四川大学华西医院神经内科, 成都 610041
摘要:
癫痫是一种以反复痫性发作为主要特征的慢性神经系统疾病,患者通常需要长期服药。妊娠期伴随的药物分布容积增加、肾血流量增加、肝脏代谢的诱导、激素水平的改变和血清蛋白浓度降低等特殊的生理状态可影响抗癫痫药的吸收、分布、代谢和清除,导致患者妊娠期癫痫发作频率增加,加大了诊疗难度。因此,如何在避免抗癫痫药相关不良妊娠结局和不良反应的同时有效控制妊娠期癫痫发作,是一个亟需解决的问题。基于此背景,本综述概括了常用抗癫痫药在妊娠期的血药浓度和(或)清除率变化及妊娠期可能影响药物代谢的因素,建议对服用拉莫三嗪、左乙拉西坦或奥卡西平的妊娠期癫痫女性患者进行常规的治疗药物监测;必要时,也可对服用托吡酯和唑尼沙胺的妊娠期癫痫女性患者进行治疗药物监测;从安全性考虑可对服用丙戊酸、卡马西平的妊娠期癫痫女性患者进行治疗药物监测。然而,目前尚需要更多高质量研究为妊娠期女性癫痫患者的用药管理提供证据。
关键词:  癫痫  抗癫痫药  妊娠  药动学  治疗药物监测
DOI:10.13748/j.cnki.issn1007-7693.2022.15.021
分类号:R969.1
基金项目:四川大学大学生创新创业计划项目(2021116560);四川大学华西医院科技成果转化基金项目(CGZH19014)
Pharmacokinetic Changes of Antiseizure Medications and Coping Strategy During Pregnancy
DUAN Yifei, LI Wanling, LAI Wanlin, CHEN Lei
Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China
Abstract:
Epilepsy is a chronic neurological condition characterized by lasting predisposition to generate spontaneous epileptic seizures, which often requires a management by lifelong intake of antiseizure medications(ASMs). The physiologic changes during pregnancy, such as the increase of distribution volume and renal blood flow, the induction of drug metabolism, the changes of hormone levels and the decrease of serum protein levels, can affect the pharmacokinetics of ASMs at any level from the absorption, distribution, metabolism, to elimination. These changes may have a direct consequence of decreased level of ASMs which leads to seizure deterioration during pregnancy. Moreover, together with many other factors, such as gene polymorphism, fetus and diet, the therapeutic effect of ASMs varies among individuals. How to achieve the balance of the benefit of achieving an adequate level of ASMs for seizure control versus minimal exposure to the fetus is an urgent question to be answered. Based on this background, this literature review summarizes the changes of level and/or clearance of commonly used ASMs during pregnancy, and strongly recommends that the monitoring of the ASMs concentrations during pregnancy is necessary, especially the newer generation ASMs such as lamotrigine, levetiracetam and oxcarbazepine. It is considerable to monitoring the level of topiramate and zonisamide and to monitoring the level of the traditional ASMs such as valproate and carbamazepine for safety. More research is needed to provide evidence for the management of women with epilepsy during pregnancy.
Key words:  epilepsy  antiepileptic drugs  pregnancy  pharmacokinetics  therapeutic drug monitoring
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