The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs

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 perfusi...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2011-07, Vol.90 (1), p.67-76
Main Authors: Hutson, JR, Garcia‐Bournissen, F, Davis, A, Koren, G
Format: Article
Language:English
Subjects:
Adult
Data Interpretation, Statistical
Female
Fetal Blood - chemistry
Humans
In Vitro Techniques
Infant, Newborn
Maternal-Fetal Exchange - physiology
Models, Biological
Models, Statistical
Perfusion
Pharmaceutical Preparations - metabolism
Placenta - blood supply
Pregnancy
Regional Blood Flow - physiology
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Summary: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. Clinical Pharmacology & Therapeutics (2011) 90 1, 67–76. doi:10.1038/clpt.2011.66
ISSN:0009-9236
1532-6535
DOI:10.1038/clpt.2011.66