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抗癫痫药物与激素避孕药之间的临床药代动力学相互作用。

Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives.

作者信息

Reddy Doodipala Samba

机构信息

Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, 228 Reynolds Medical Building, College Station, TX 77843, USA, Tel.: +1 979 862 2852, ,

出版信息

Expert Rev Clin Pharmacol. 2010 Mar 1;3(2):183-192. doi: 10.1586/ecp.10.3.

Abstract

Contraceptive management in women with epilepsy is critical owing to the potential maternal and fetal risks if contraception or seizure management fails. This article briefly describes the pharmacokinetic interactions between antiepileptic drugs (AEDs) and hormonal contraceptives and the rational strategies that may overcome these risks. Hormonal contraception, including the use of oral contraceptives (OCs), is widely used in many women with epilepsy - there is no strong evidence of seizures worsening with their use. AEDs are the mainstay for seizure control in women with epilepsy. However, there are many factors to consider in the choice of AED therapy and hormonal contraception, since some AEDs can reduce the efficacy of OCs owing to pharmacokinetic interactions. Estrogens and progestogens are metabolized by cytochrome P450 3A4. AEDs, such as phenytoin, phenobarbital, carbamazepine, felbamate, topiramate, oxcarbazepine and primidone, induce cytochrome P450 3A4, leading to enhanced metabolism of either or both the estrogenic and progestogenic component of OCs, thereby reducing their efficacy in preventing pregnancy. OCs can also decrease the concentrations of AEDs such as lamotrigine and, thereby, increase the risk of seizures. Increased awareness of AED interactions may help optimize seizure therapy in women with epilepsy.

摘要

癫痫女性的避孕管理至关重要,因为如果避孕或癫痫管理失败,可能会对母婴造成风险。本文简要描述了抗癫痫药物(AEDs)与激素避孕药之间的药代动力学相互作用以及可能克服这些风险的合理策略。激素避孕,包括口服避孕药(OCs)的使用,在许多癫痫女性中广泛应用——没有强有力的证据表明使用这些药物会使癫痫发作恶化。AEDs是癫痫女性控制癫痫发作的主要手段。然而,在选择AED治疗和激素避孕时需要考虑许多因素,因为一些AEDs由于药代动力学相互作用会降低OCs的疗效。雌激素和孕激素由细胞色素P450 3A4代谢。苯妥英、苯巴比妥、卡马西平、非氨酯、托吡酯、奥卡西平和扑米酮等AEDs会诱导细胞色素P450 3A4,导致OCs的雌激素和孕激素成分之一或两者的代谢增强,从而降低其预防妊娠的效果。OCs也会降低拉莫三嗪等AEDs的浓度,从而增加癫痫发作的风险。提高对AED相互作用的认识可能有助于优化癫痫女性的癫痫治疗。

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