TY - JOUR

T1 - Placental transfer and vascular effects of pharmaceutical drugs in the human placenta ex vivo

T2 - A review

AU - van Hove, H

AU - Mathiesen, L

AU - Freriksen, J J M

AU - Vähäkangas, K

AU - Colbers, A

AU - Brownbill, P

AU - Greupink, R

N1 - Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2022

Y1 - 2022

N2 - At least 80% of pregnant woman in Europe use at least one medication during their pregnancy. The majority of these drugs are prescribed off-label. A better understanding of drug transport and effects in the placenta can provide an improved pharmacological basis to rationalize drug and dose selection for prescription. Here we provide a narrative review of studies that used the ex vivo placenta perfusion model to study placental drug transport and vascular effects of pharmaceuticals. For studies on placental transfer, we found that the methodology used varied substantially between studies as well as the way in which data was reported. Across the different therapeutic groups, ex vivo measurements of transfer generally corresponded well to in vivo findings. Still, further standardization of the perfusion technique would facilitate a broader use of perfusion data, e.g. in the context of quantitative systems pharmacology models as has been explored in recent years. Only few studies investigated the effects of drugs on the vascular tone using the ex vivo dual-side perfusion model. The model was particularly applied to study vasodilatory effects of pharmaceuticals in the fetoplacental circulation. In conclusion, the ex vivo dually perfused human cotyledon provides a relevant system to gain insights in placental drug disposition and study effects on the fetoplacental vasculature.

AB - At least 80% of pregnant woman in Europe use at least one medication during their pregnancy. The majority of these drugs are prescribed off-label. A better understanding of drug transport and effects in the placenta can provide an improved pharmacological basis to rationalize drug and dose selection for prescription. Here we provide a narrative review of studies that used the ex vivo placenta perfusion model to study placental drug transport and vascular effects of pharmaceuticals. For studies on placental transfer, we found that the methodology used varied substantially between studies as well as the way in which data was reported. Across the different therapeutic groups, ex vivo measurements of transfer generally corresponded well to in vivo findings. Still, further standardization of the perfusion technique would facilitate a broader use of perfusion data, e.g. in the context of quantitative systems pharmacology models as has been explored in recent years. Only few studies investigated the effects of drugs on the vascular tone using the ex vivo dual-side perfusion model. The model was particularly applied to study vasodilatory effects of pharmaceuticals in the fetoplacental circulation. In conclusion, the ex vivo dually perfused human cotyledon provides a relevant system to gain insights in placental drug disposition and study effects on the fetoplacental vasculature.

U2 - 10.1016/j.placenta.2022.03.128

DO - 10.1016/j.placenta.2022.03.128

M3 - Review

C2 - 35397340

VL - 122

SP - 29

EP - 45

JO - Placenta

JF - Placenta

SN - 0143-4004

ER -