The impact of pregnancy on the pharmacokinetics of antiseizure medications: A systematic review and meta-analysis of data from 674 pregnancies

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2024-05-16 DOI:10.1016/j.pnpbp.2024.111030

Georgios Schoretsanitis , Kristina M. Deligiannidis , Nicholas Kasperk , Chiara Theresa Schmidt , Sarah Kittel-Schneider , Peter Ter Horst , Maya Berlin , Elkana Kohn , Eline M.P. Poels , Deepti Zutshi , Torbjörn Tomson , Olav Spigset , Michael Paulzen

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引用次数: 0

Abstract

Objective

Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics.

Methods

A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines.

Results

A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07–2.45, 0.42, range 0.08–0.82 and 0.52, range 0.04–2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10⁻³, 95%CI = -16.08 to −8.58 × 10⁻³ (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to −4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to −0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10⁻³ (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10⁻³, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5.

Conclusions

Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.

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妊娠对抗癫痫药物药代动力学的影响：对 674 例妊娠数据的系统回顾和荟萃分析

目的越来越多的证据表明，妊娠期的生理变化可能会影响抗癫痫药物（ASM）的药代动力学，从而影响治疗效果。本研究旨在量化妊娠对 ASM 药代动力学的影响。方法于 2022 年 11 月在 PubMed/EMBASE 上进行了系统性文献检索，并于 2023 年 8 月更新了相关研究，以比较相同个体在妊娠期和孕前/产后期间的 ASM 水平。我们估算了怀孕三个月与基线之间的变化比率。我们还进行了随机效应荟萃分析，计算剂量调整后血浆浓度（C/D 比值）的平均差（MDs）和 95% 置信区间（95%CIs）的时点间差异。结果共纳入了 65 项研究，这些研究调查了 674 例妊娠中的 15 种 ASM。拉莫三嗪、奥卡西平和左乙拉西坦的差异最大（改变比分别为 0.42（范围 0.07-2.45）、0.42（范围 0.08-0.82）和 0.52（范围 0.04-2.77））：因此，拉莫三嗪、左乙拉西坦和奥卡西平的主要代谢产物单羟基卡西平在妊娠第 3 个月的 C/D 水平较低（MD = -12.33 × 10-3, 95%CI = -16.08 to -8.58 × 10-3 (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively)，而奥卡西平则没有（MD = 1.16 × 10-3 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10-3, p = 0.10）。拉莫三嗪、奥卡西平（和单羟基卡西平）和左乙拉西坦的结论数据显示，妊娠期间的药代动力学发生了重大变化，这表明治疗药物监测对于协助临床医生优化治疗效果非常重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Progress in Neuro-Psychopharmacology & Biological Psychiatry 医学-精神病学

CiteScore

12.00

自引率

1.80%

发文量

153

审稿时长

56 days

期刊介绍： Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.