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The AAPS Journal

, 21:67 | Cite as

Mind the Gaps: Ontogeny of Human Brain P-gp and Its Impact on Drug Toxicity

  • Jean-Marie NicolasEmail author
  • Elizabeth C. M. de Lange
Review Article

Abstract

Available data on human brain P-glycoprotein ontogeny during infancy and childhood are limited. This review discusses the current body of data relating to maturation of human brain P-glycoprotein including transporter expression levels in post-mortem human brain samples, in vivo transporter activity using probe substrates, surrogate marker endpoints, and extrapolations from animal models. Overall, the data tend to confirm that human brain P-glycoprotein activity keeps developing after birth, although with a developmental time frame that remains unclear. This knowledge gap is a concern given the critical role of brain P-glycoprotein in drug safety and efficacy, and the vulnerable nature of the pediatric population. Future research could include the measurement of brain P-glycoprotein activity across age groups using positron emission tomography or central pharmacodynamic responses. For now, caution is advised when extrapolating adult data to children aged younger than 2 years for drugs with P-glycoprotein-dependent central nervous system activity.

KEY WORDS

blood-brain barrier brain ontogeny pediatric P-glycoprotein 

Notes

Acknowledgments

The authors would like to acknowledge Laura Griffin, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc for editing assistance that was funded by UCB Pharma in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Quantitative Pharmacology DMPK DepartmentUCB BioPharmaBraine L’AlleudBelgium
  2. 2.Research Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug ResearchLeiden UniversityLeidenThe Netherlands

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