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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Methodological Approaches to Evaluate Fetal Drug Exposure

Author(s): Naïm Bouazza, Frantz Foissac, Déborah Hirt, Saïk Urien, Sihem Benaboud, Gabrielle Lui and Jean-Marc Treluyer*

Volume 25, Issue 5, 2019

Page: [496 - 504] Pages: 9

DOI: 10.2174/1381612825666190319102812

Price: $65

Abstract

Background: Drug prescriptions are usual during pregnancy, however, women and their fetuses still remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies.

Methods: To summarize the different methodologies developed towards the prediction of fetal drug exposure.

Results: Neonatal cord blood concentration is the most specific measurement of the transplacental drug transfer at the end of pregnancy. Using the cord blood and mother drug concentrations altogether, drug exchanges between the mother and fetus can be modeled and quantified via a population pharmacokinetic analysis. Thereafter, it is possible to estimate the fetus exposure and the fetus-to-mother exposure ratio. However, the prediction of placental transfer before any administration to pregnant women is desirable. Animal studies remain difficult to interpret due to structural and functional inter-species placenta differences. The ex-vivo perfusion of the human placental cotyledon is the method of reference to study the human placental transfer of drugs because it is thought to mimic the functional placental tissue. However, extrapolation of data to in vivo situation remains difficult. Some research groups have extensively worked on physiologically based models (PBPK) to predict fetal drug exposure and showed very encouraging results.

Conclusion: PBPK models appeared to be a very promising tool in order to predict fetal drug exposure in-silico. However, these models mainly picture the end of pregnancy and knowledge regarding both, development of the placental permeability and transporters is strongly needed.

Keywords: Pregnancy, fetal drug exposure, pharmacokinetics, placental drug transfer, human placental cotyledon, permeability.

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