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Barriers to Drug Distribution into the Perinatal and Postnatal Brain

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  • Theme: The Use of Therapeutics in Pregnancy and Lactation
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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.

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Abbreviations

ADR:

Adverse drug reaction

BBB:

Blood-brain barrier

BCSFB:

Blood-CSF barrier

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

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Acknowledgements and disclosures

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

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Authors and Affiliations

  1. FLUID Team, Lyon Neurosciences Research Center, INSERM U1028 CRNS UMR 5292, Université Claude Bernard Lyon-1, 69008, Lyon, France

    Jean-François Ghersi-Egea, Elodie Saudrais & Nathalie Strazielle

  2. Blood-Brain Interfaces Exploratory Platform BIP, Lyon Neurosciences Research Center, 69008, Lyon, France

    Jean-François Ghersi-Egea, Elodie Saudrais & Nathalie Strazielle

  3. Brain-I, 69008, Lyon, France

    Nathalie Strazielle

Authors
  1. Jean-François Ghersi-Egea
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  2. Elodie Saudrais
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  3. Nathalie Strazielle
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Correspondence to Jean-François Ghersi-Egea.

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Guest Editor: Sara Eyal

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Ghersi-Egea, JF., Saudrais, E. & Strazielle, N. Barriers to Drug Distribution into the Perinatal and Postnatal Brain. Pharm Res 35, 84 (2018). https://doi.org/10.1007/s11095-018-2375-8

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