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Pharmaceutical Research

, 35:84 | Cite as

Barriers to Drug Distribution into the Perinatal and Postnatal Brain

  • Jean-François Ghersi-Egea
  • Elodie Saudrais
  • Nathalie Strazielle
Expert Review Theme: The Use of Therapeutics in Pregnancy and Lactation
Part of the following topical collections:
  1. The Use of Therapeutics in Pregnancy and Lactation

Abstract

Drug bioavailability to the developing brain is a major concern in the treatment of neonates and infants as well as pregnant and breast-feeding women. Central adverse drug reactions can have dramatic consequences for brain development, leading to major neurological impairment. Factors setting the cerebral bioavailability of drugs include protein-unbound drug concentration in plasma, local cerebral blood flow, permeability across blood-brain interfaces, binding to neural cells, volume of cerebral fluid compartments, and cerebrospinal fluid secretion rate. Most of these factors change during development, which will affect cerebral drug concentrations. Regarding the impact of blood-brain interfaces, the blood-brain barrier located at the cerebral endothelium and the blood-cerebrospinal fluid barrier located at the choroid plexus epithelium both display a tight phenotype early on in embryos. However, the developmental regulation of some multispecific efflux transporters that also limit the entry of numerous drugs into the brain through barrier cells is expected to favor drug penetration in the neonatal brain. Finally, drug cerebral bioavailability is likely to be affected following perinatal injuries that alter blood-brain interface properties. A thorough investigation of these mechanisms is mandatory for a better risk assessment of drug treatments in pregnant or breast-feeding women, and in neonate and pediatric patients.

KEY WORDS

blood-brain barrier cerebrospinal fluid choroid plexus development efflux transporters 

Abbreviations

ADR

Adverse drug reaction

BBB

Blood-brain barrier

BCSFB

Blood-CSF barrier

CNS

Central nervous system

CSF

Cerebrospinal fluid

Notes

Acknowledgements and disclosures

This work was funded by ANR-10-IBHU-0003 CESAME grant.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.FLUID Team, Lyon Neurosciences Research Center, INSERM U1028 CRNS UMR 5292Université Claude Bernard Lyon-1LyonFrance
  2. 2.Blood-Brain Interfaces Exploratory Platform BIPLyon Neurosciences Research CenterLyonFrance
  3. 3.Brain-ILyonFrance

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