Certara UK Limited (Simcyp Division), Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK.
Clin Pharmacokinet. 2021 Jun;60(6):741-757. doi: 10.1007/s40262-020-00973-0. Epub 2021 Jan 24.
Fetal circulation is unique and the parameters describing hemodynamic status during development are critical for constructing a fetal physiologically based pharmacokinetic model. To date, a comprehensive review of circulatory changes during fetal development, with a specific focus on developing these models, has not been reported. The objective of this work was to collate, analyze, and mathematically describe physiological information on fetal cardiac output and tissue blood flows during development.
A comprehensive literature search was carried out to collate and evaluate the changes to fetal cardiac output and fetal tissue blood flows during growth. The collated data were assessed, integrated, and analyzed to establish continuous mathematical functions describing the average parameter changes and variability during development.
Data were available for fetal cardiac output (14 Doppler studies), blood flow through the fetal umbilical vein (15 studies), ductus venosus (6 studies), liver veins (5 studies), brain (4 studies), lungs (5 studies), and kidneys (2 studies). Fetal cardiac output is described as either an age- or weight-dependent function. The latter is preferred as it generates an individualized cardiac output that is correlated to the fetal body weight. Blood flow as a proportion of fetal cardiac output to the liver, placenta, brain, kidneys, and lungs was age varying, whilst for the adipose, bone, heart, muscle, and skin the blood flow proportions were fixed. The pattern of change (with respect to direction and pace) for each of these parameters was different.
Despite limitations in the availability of some values, the collected data provide a useful resource for fetal physiologically based pharmacokinetic modeling. Potential applications of these data include predicting xenobiotic exposure and risk assessment in the fetus following the administration of maternally dosed drugs or unintended exposure to environmental toxicants.
胎儿循环具有独特性，描述发育过程中血液动力学状态的参数对于构建胎儿生理基础药代动力学模型至关重要。迄今为止，尚未有关于胎儿发育过程中循环变化的全面综述，特别是关于这些模型的发展。本研究的目的是整理、分析和数学描述胎儿心输出量和组织血流在发育过程中的生理信息。
进行了全面的文献检索，以整理和评估胎儿心输出量和胎儿组织血流在生长过程中的变化。对整理的数据进行评估、整合和分析，建立描述发育过程中平均参数变化和变异性的连续数学函数。
有 14 项多普勒研究提供了胎儿心输出量的数据，15 项研究提供了胎儿脐静脉血流量的数据，6 项研究提供了静脉导管血流量的数据，5 项研究提供了肝静脉血流量的数据，4 项研究提供了大脑血流量的数据，5 项研究提供了肺部血流量的数据，2 项研究提供了肾脏血流量的数据。胎儿心输出量被描述为年龄相关或体重相关的函数。后者更受欢迎，因为它生成了与胎儿体重相关的个体心输出量。肝脏、胎盘、大脑、肾脏和肺部的血流量占胎儿心输出量的比例随年龄而变化，而脂肪、骨骼、心脏、肌肉和皮肤的血流量比例是固定的。这些参数的变化模式（方向和速度）各不相同。
尽管某些值的可用性存在局限性，但收集的数据为胎儿生理基础药代动力学建模提供了有用的资源。这些数据的潜在应用包括预测母体给药药物或意外暴露于环境毒物后胎儿的外源性物质暴露和风险评估。
