Table_1_A systematic review of pregnancy-related clinical intervention of drug regimens due to pharmacokinetic reasons.XLSX

Background and objectivePublished works have discussed the pharmacokinetic interactions of drugs with pregnancy, but none comprehensively identify all the approved United States Food and Drug Administration (FDA) and European Medicines Administration (EMA) drugs that have a pregnancy-related intervention. The objective of this systematic review is to comprehensively identify medications that have clinically meaningful interventions due to pharmacokinetic reasons.
MethodsAn in-depth search of clinical data using the PDR3D: Reed Tech Navigator™ for Drug Labels was conducted from 1 June to 12 August 2022. The PDR3D was analyzed using the search terms “pregnant” and “pregnancy” within the proper label section. Regarding the US labels, the terms were searched under the “dosage and administration” section, whereas with the EU labels, the terms were searched within the “posology and method of administration” section. If a finding was discovered within the search, the rest of the label was analyzed for further information. Clinical relevance was based on whether an intervention was needed.
ResultsUsing the search strategy, 139 US and 20 EU medications were found to have clinically meaningful interventions in pregnancy. The most common explanations for clinical relevance included hepatic metabolism, protein binding, renal elimination, and P-gp influence. Of the US labels: 40 were found to undergo hepatic metabolism, 11 were found to be influenced by renal elimination, 12 were found to be influenced by protein binding, 7 were found to be influenced by P-gp, and the remaining drugs required further research. Of the EU labels: 11 were found to undergo hepatic metabolism, 3 were found to be influenced by renal elimination, 3 were found to be influenced by protein binding, 1 was found to be influenced by P-gp, and the remaining drugs required further research.
ConclusionThis comprehensive review of clinically relevant interventions in pregnancy will potentially aid in the treatment of pregnant females when they are undergoing therapy, provide intervention and dosing guidance for physicians, and save time for prescribers and pharmacists. Advances in non-clinical predictions for pregnancy dosing may guide the need for a future clinical evaluation.

背景与目标
已有文献探讨了药物与妊娠的药代动力学相互作用，但尚无研究全面识别美国食品药品监督管理局（FDA）与欧洲药品管理局（EMA）获批的所有存在妊娠相关干预措施的药品。本系统评价的目标为全面识别因药代动力学原因需要采取具有临床意义的干预措施的药物。
方法
2022年6月1日至8月12日，采用PDR3D：Reed Tech Navigator™药品标签数据库对临床数据进行深度检索。检索时在药品标签的对应章节中使用“妊娠”“怀孕”作为检索词；针对美国药品标签，检索章节为“给药剂量与用法”，针对欧盟药品标签，检索章节为“给药方案与用法”。若检索到相关结果，则进一步分析该标签其余部分以获取更多信息。临床相关性依据是否需要采取干预措施进行判定。
结果
采用本次检索策略，共筛选得到139种美国获批药品、20种欧盟获批药品，其在妊娠人群中存在具有临床意义的干预措施。导致其具备临床相关性的最常见机制包括肝脏代谢、蛋白结合、肾脏清除以及P-糖蛋白（P-gp）的影响。其中美国获批药品中，40种经肝脏代谢、11种受肾脏清除影响、12种受蛋白结合影响、7种受P-糖蛋白影响，其余药品尚需进一步研究；欧盟获批药品中，11种经肝脏代谢、3种受肾脏清除影响、3种受蛋白结合影响、1种受P-糖蛋白影响，其余药品尚需进一步研究。
结论
本项针对妊娠人群临床相关干预措施的全面系统评价，可为妊娠女性的临床治疗提供参考，为医师提供干预措施与给药方案指导，同时为处方医师与药师节省工作时间。妊娠给药的非临床预测研究进展，可为未来开展临床评估提供指引。