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Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal-Fetal Drug Transfer.

  • Dallmann A Pediatric Pharmacology and Pharmacometrics Research Center, University Children's Hospital Basel (UKBB), Switzerland.
  • Liu XI Division of Clinical Pharmacology, Children's National Medical Center, Washington, DC, USA.
  • Burckart GJ US Food and Drug Administration, Office of Clinical Pharmacology, Silver Spring, MD, USA.
  • van den Anker J Pediatric Pharmacology and Pharmacometrics Research Center, University Children's Hospital Basel (UKBB), Switzerland.
  • 2019-09-11
Published in:
  • Journal of clinical pharmacology. - 2019
PBPK
fetal medicine
modeling and simulation
obstetrics
transporters
Biological Transport
Female
Fetus
Humans
Maternal-Fetal Exchange
Membrane Transport Proteins
Models, Biological
Placenta
Pregnancy
English Tremendous efforts have been directed to investigate the ontogeny of drug transporters in fetuses, neonates, infants, and children based on their importance for understanding drug pharmacokinetics. During development (ie, in the fetus and newborn infant), there is special interest in transporters expressed in the placenta that modulate placental drug transfer. Many of these transporters can decrease or increase drug concentrations in the fetus and at birth, stressing the relevance of elucidating expression in the placenta and potential gestational age-dependent changes therein. Hence, the main objective of this review was to summarize the current knowledge about expression and ontogeny of transporters in the human placenta in healthy pregnant women. In addition, various in vitro, ex vivo, and in silico models that can be used to investigate placental drug transfer, namely, placental cancer cell lines, ex vivo cotyledon perfusion experiments, and physiologically based pharmacokinetic (PBPK) models, are discussed together with their advantages and shortcomings. A particular focus was placed on PBPK models because these models can integrate different types of information, such as expression data, ontogeny information, and observations obtained from the ex vivo cotyledon perfusion experiment. Such a mechanistic modeling framework may leverage the available information and ultimately help to improve knowledge about the adequacy and safety of pharmacotherapy in pregnant women and their fetuses.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/102546
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