与妊娠有关的荷尔蒙和生理变化对抗癫痫药物的影响:专家观点。

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Expert Review of Clinical Pharmacology Pub Date : 2024-08-01 Epub Date: 2024-05-21 DOI:10.1080/17512433.2024.2356617
Denise Li, Susannah Franco, Page B Pennell
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引用次数: 0

摘要

导言:癫痫是一种无诱因反复发作的疾病,影响着全球约 1500 万育龄人群。癫痫患者需要每天定期服用抗癫痫药物(ASMs)。此外,ASMs 还可用于其他神经精神适应症(如躁郁症、疼痛、偏头痛),美国有超过 2% 的孕妇在产前接触过 ASMs:ASM 的浓度受孕期激素和生理变化的影响,包括肾脏和肝脏血流量增加、蛋白结合力下降以及酶活性变化。清除率的变化通常在分娩后几周内逆转。在妊娠期间,许多 ASMs,如拉莫三嗪、左乙拉西坦和奥卡西平,应监测血清浓度并增加剂量,以维持癫痫发作控制的个体化目标范围。通过葡萄糖醛酸化代谢的 ASM(主要是拉莫三嗪)在整个孕期的清除率会显著增加,到分娩时需要的每日剂量约为孕前的 3 倍。产后,ASM 的剂量通常会在几周内减少,以防止药物中毒:专家意见:未来,针对各种 ASM 开发基于生理学的药代动力学模型可能会使妊娠期经验性剂量调整成为可能,而无需频繁进行治疗药物监测。
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The impact of pregnancy-related hormonal and physiological changes on antiseizure medications: expert perspective.

Introduction: Epilepsy is a disorder of recurrent, unprovoked seizures affecting approximately 15 million individuals of childbearing potential worldwide. Patients with epilepsy rely on regular daily therapy with antiseizure medications (ASMs). Furthermore, ASMs are also prescribed for other neuropsychiatric indications (e.g. bipolar disorder, pain, migraines) with over 2% of the pregnancies in the United States involving prenatal exposure to ASMs.

Areas covered: ASM concentrations are affected by hormonal and physiological changes in pregnancy, including increases in renal and hepatic blood flow, decreased protein binding, and changes in enzyme activity. Clearance changes typically reverse within a few weeks after delivery. During pregnancy, many ASMs, such as lamotrigine, levetiracetam, and oxcarbazepine, should have serum concentrations monitored and doses increased to maintain the individualized target range for seizure control. ASMs metabolized via glucuronidation, primarily lamotrigine, undergo marked increases in clearance throughout pregnancy, requiring about 3-fold the pre-pregnancy daily dose by delivery. Postpartum, ASM doses are usually decreased over several weeks to prevent drug toxicity.

Expert opinion: In the future, the development of a physiologically-based pharmacokinetic model for various ASMs may enable empiric dose adjustments in pregnancy without the difficulties of frequent therapeutic drug monitoring.

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来源期刊
Expert Review of Clinical Pharmacology
Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.30
自引率
2.30%
发文量
127
期刊介绍: Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.
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