A Review on the Molecular Mechanisms Involved in the Placental Barrier for Drugs

Jose   J.G.   Marin; Oscar      Briz; Maria   A.   Serrano

Abstract

The placenta has traditionally been considered as a highly permeable organ for a large variety of substances with diverse molecular structures that are readily able to cross it from the maternal blood to reach the foetus. This has recommended limiting the use of drugs during pregnancy as far as possible. However, our present knowledge points to the existence of different systems, including plasma membrane carriers, biotransforming enzymes, and export pumps, that determine the selectivity and efficacy of the so-called placental barrier. A good understanding of the molecular bases of these processes and their regulation is crucial: i) to predict interactions between drug-drug, drug-endogenous substances and drug-food components, ii) to analyse the relevance of polymorphisms in the inter-individual variability of conceptus sensitivity to drugs, and iii) to develop novel pharmacological strategies aimed at delivering medicinal drugs to pregnant women, simultaneously minimising the risk of foetal exposure to active agents, and to specifically target drugs to the placenta and / or foetus. The present review does not attempt to offer a complete list of the available medicinal compounds and their ability to cross the placenta but instead to provide the reader with an up-to-date overview of the mechanisms involved in carrying out or preventing the transfer of active drugs across the placenta.

Keywords: placental barrier, plasma membrane carriers, biotransforming enzymes, export pumps

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