Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Clin Pharmacokinet. 2024 May;63(5):589-622. doi: 10.1007/s40262-024-01370-7. Epub 2024 Apr 7.
Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy.
A systematic literature search was carried out in PubMed and Embase on 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available.
A total of 42 relevant articles were included, of which eight discussed adalimumab, three certolizumab pegol, five eculizumab, one golimumab, 12 infliximab (IFX), two natalizumab, one canakinumab, one omalizumab, five tocilizumab, eight ustekinumab, and five vedolizumab. One of the 42 studies reported information on clearance (CL) and volume of distribution (VD) of IFX; all other studies only reported on serum concentrations in the pre-pregnancy state, different trimesters, and the postpartum period. For all of the assessed mAbs except IFX, serum concentrations were similar to concentrations in the pre-pregnancy state or modestly decreased. In contrast, IFX trough concentrations generally increased in the second and third trimesters in comparison to the non-pregnant state.
Available information suggests that the anatomical and physiological changes throughout pregnancy may have meaningful effects on the PK of mAbs. For most mAbs (not IFX), modestly higher dosing (per mg) maybe needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy.
尽管关于妊娠期间单克隆抗体（mAbs）的药代动力学（PK）信息很少，但多种 mAbs 正被用于各种适应证的妊娠期间。本系统文献回顾的目的是描述 mAbs 在整个妊娠期间的 PK 特征。
我们于 2023 年 4 月 21 日在 PubMed 和 Embase 中进行了系统文献检索。当有关于孕妇中 mAbs 的 PK 或暴露参数的信息时，纳入相关文章。
共纳入 42 篇相关文章，其中 8 篇讨论了阿达木单抗，3 篇讨论了培塞利珠单抗，5 篇讨论了依库珠单抗，1 篇讨论了戈利木单抗，12 篇讨论了英夫利昔单抗（IFX），2 篇讨论了那他珠单抗，1 篇讨论了卡那奴单抗，1 篇讨论了奥马珠单抗，5 篇讨论了托珠单抗，8 篇讨论了乌司奴单抗，5 篇讨论了维得利珠单抗。42 项研究中的 1 项报告了 IFX 的清除率（CL）和分布容积（VD）信息；所有其他研究仅报告了妊娠前状态、不同妊娠期间和产后的血清浓度。除 IFX 外，所有评估的 mAbs 的血清浓度与妊娠前状态或适度降低的浓度相似。相比之下，IFX 的谷浓度在第二和第三孕期与非妊娠状态相比通常增加。
现有信息表明，妊娠期间的解剖和生理变化可能对 mAbs 的 PK 产生有意义的影响。对于大多数 mAbs（IFX 除外），与妊娠前相比，可能需要在妊娠期间适度增加（每毫克）剂量，以维持相似的血清暴露。
