Tomson Torbjörn, Battino Dina
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Clin Pharmacokinet. 2007;46(3):209-19. doi: 10.2165/00003088-200746030-00002.
The treatment of epilepsy in pregnancy is particularly challenging in that the fetal and maternal risks associated with maternal seizures need to be balanced against the potential teratogenic effects of antiepileptic drugs (AEDs). Pregnancy is known to affect the pharmacokinetics of older-generation AEDs. Understanding such alterations is important in the effort to optimise drug therapy since they may affect seizure control as well as fetal drug exposure. Therapeutic drug monitoring has therefore been recommended to control for changes in the disposition of the older-generation AEDs during pregnancy. Much less is known about gestation-induced alterations in the pharmacokinetics of the newer AEDs that have been introduced in the last 15 years. Lamotrigine is by far the most extensively studied of the newer AEDs. Pronounced alterations have been reported in the apparent clearance of lamotrigine, with an increase of >300% from baseline in late pregnancy in some patients on monotherapy, most likely due to enhanced metabolism. The available data suggest that the corresponding decline in plasma concentrations can be associated with loss of seizure control. More limited data indicate that a similar decline in plasma concentrations of the active monohydroxy derivative of oxcarbazepine may occur in late pregnancy. Preliminary experience also suggests that a significant fall in plasma concentrations of levetiracetam may occur during pregnancy. No systematic information is available on the pharmacokinetics during pregnancy of other newer AEDs (e.g. gabapentin, pregabalin, tiagabine, topiramate or zonisamide). Given the importance of maintaining optimal treatment of epilepsy during pregnancy, therapeutic drug monitoring appears to be justified for lamotrigine and oxcarbazepine in particular. Systematic studies of the effects of pregnancy on the pharmacokinetics of the other newer-generation AEDs are urgently needed.
孕期癫痫的治疗极具挑战性，因为需要在与母亲癫痫发作相关的胎儿和母亲风险与抗癫痫药物（AEDs）的潜在致畸作用之间进行权衡。众所周知，怀孕会影响第一代AEDs的药代动力学。了解这些变化对于优化药物治疗很重要，因为它们可能会影响癫痫控制以及胎儿的药物暴露。因此，建议进行治疗药物监测，以控制孕期第一代AEDs处置的变化。对于过去15年引入的新型AEDs，孕期引起的药代动力学变化了解得要少得多。拉莫三嗪是新型AEDs中研究最广泛的。据报道，拉莫三嗪的表观清除率有显著变化，一些接受单药治疗的患者在妊娠晚期其清除率较基线增加>300%，这很可能是由于代谢增强所致。现有数据表明，血浆浓度的相应下降可能与癫痫控制丧失有关。更有限的数据表明，奥卡西平的活性单羟基衍生物在妊娠晚期血浆浓度可能会出现类似下降。初步经验还表明，左乙拉西坦在孕期血浆浓度可能会显著下降。对于其他新型AEDs（如加巴喷丁、普瑞巴林、噻加宾、托吡酯或唑尼沙胺）孕期药代动力学尚无系统信息。鉴于孕期维持癫痫最佳治疗的重要性，治疗药物监测对于拉莫三嗪和奥卡西平尤其合理。迫切需要对孕期对其他新一代AEDs药代动力学的影响进行系统研究。
