Hudson Rachel E, Metz Torri D, Ward Robert M, McKnite Autumn M, Enioutina Elena Y, Sherwin Catherine M, Watt Kevin M, Job Kathleen M
Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, The University of Utah, Salt Lake City, UT, United States.
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, School of Medicine, The University of Utah, Salt Lake City, UT, United States.
Front Pharmacol. 2023 Mar 23;14:1111601. doi: 10.3389/fphar.2023.1111601. eCollection 2023.
Prescription drug use is prevalent during pregnancy, yet there is limited knowledge about maternal-fetal safety and efficacy of this drug use because pregnant individuals have historically been excluded from clinical trials. Underrepresentation has resulted in a lack of data available to estimate or predict fetal drug exposure. Approaches to study fetal drug pharmacology are limited and must be evaluated for feasibility and accuracy. Anatomic and physiological changes throughout pregnancy fluctuate based on gestational age and can affect drug pharmacokinetics (PK) for both mother and fetus. Drug concentrations have been studied throughout different stages of gestation and at or following delivery in tissue and fluid biospecimens. Sampling amniotic fluid, umbilical cord blood, placental tissue, meconium, umbilical cord tissue, and neonatal hair present surrogate options to quantify and characterize fetal drug exposure. These sampling methods can be applied to all therapeutics including small molecule drugs, large molecule drugs, conjugated nanoparticles, and chemical exposures. Alternative approaches to determine PK have been explored, including physiologically based PK modeling, methods, and traditional animal models. These alternative approaches along with convenience sampling of tissue or fluid biospecimens can address challenges in studying maternal-fetal pharmacology. In this narrative review, we 1) present an overview of the current understanding of maternal-fetal drug exposure; 2) discuss biospecimen-guided sampling design and methods for measuring fetal drug concentrations throughout gestation; and 3) propose methods for advancing pharmacology research in the maternal-fetal population.
孕期使用处方药的情况很普遍，但由于孕妇历来被排除在临床试验之外，关于孕期用药对母婴的安全性和有效性的了解有限。代表性不足导致缺乏可用于估计或预测胎儿药物暴露的数据。研究胎儿药物药理学的方法有限，必须对其可行性和准确性进行评估。孕期的解剖学和生理学变化会根据孕周而波动，并可能影响母亲和胎儿的药物药代动力学（PK）。已在妊娠的不同阶段以及分娩时或分娩后对组织和体液生物样本中的药物浓度进行了研究。采集羊水、脐带血、胎盘组织、胎粪、脐带组织和新生儿毛发是量化和表征胎儿药物暴露的替代选择。这些采样方法可应用于所有治疗药物，包括小分子药物、大分子药物、共轭纳米颗粒和化学暴露物。已经探索了确定药代动力学的替代方法，包括基于生理学的药代动力学建模、方法和传统动物模型。这些替代方法以及对组织或体液生物样本的便利采样可以解决研究母婴药理学方面的挑战。在这篇叙述性综述中，我们1）概述目前对母婴药物暴露的理解；2）讨论生物样本指导的采样设计和在整个孕期测量胎儿药物浓度的方法；3）提出推进母婴群体药理学研究的方法。
