Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
Clin Pharmacol Ther. 2011 Jul;90(1):67-76. doi: 10.1038/clpt.2011.66. Epub 2011 May 11.
Dual perfusion of a single placental lobule is the only experimental model to study human placental transfer of substances in organized placental tissue. To date, there has not been any attempt at a systematic evaluation of this model. The aim of this study was to systematically evaluate the perfusion model in predicting placental drug transfer and to develop a pharmacokinetic model to account for nonplacental pharmacokinetic parameters in the perfusion results. In general, the fetal-to-maternal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant. After modeling for differences in maternal and fetal/neonatal protein binding and blood pH, the perfusion results were able to accurately predict in vivo transfer at steady state (R² = 0.85, P < 0.0001). Placental perfusion experiments can be used to predict placental drug transfer when adjusting for extra parameters and can be useful for assessing drug therapy risks and benefits in pregnancy.
双灌注单个胎盘小叶是研究物质在胎盘组织中转运的唯一实验模型。迄今为止，尚未有人尝试对该模型进行系统评估。本研究旨在系统评估该模型在预测胎盘药物转运中的作用，并开发一种药代动力学模型来解释灌注结果中非胎盘药代动力学参数。一般来说，胎盘灌注实验与婴儿分娩时体内样本的胎儿-母体药物浓度比值相匹配。对母体和胎儿/新生儿蛋白结合和血液 pH 差异进行建模后，灌注结果能够准确预测稳态下的体内转运（R²=0.85，P<0.0001）。当调整额外参数时，胎盘灌注实验可用于预测胎盘药物转运，并且对于评估妊娠期间药物治疗的风险和益处可能很有用。
