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Research ArticleSpecial Section on Pediatric Drug Disposition and Pharmacokinetics—Minireview

Ontogeny of Hepatic Drug Transporters and Relevance to Drugs Used in Pediatrics

Yasmine Elmorsi, Jill Barber and Amin Rostami-Hodjegan
Drug Metabolism and Disposition July 2016, 44 (7) 992-998; DOI: https://doi.org/10.1124/dmd.115.067801
Yasmine Elmorsi
Manchester Pharmacy School, University of Manchester, Manchester, United Kingdom (Y.E., J.B., A.R.-H.); and Simcyp Limited (a Certara Company) Sheffield, United Kingdom (A.R.-H.).
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Jill Barber
Manchester Pharmacy School, University of Manchester, Manchester, United Kingdom (Y.E., J.B., A.R.-H.); and Simcyp Limited (a Certara Company) Sheffield, United Kingdom (A.R.-H.).
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Amin Rostami-Hodjegan
Manchester Pharmacy School, University of Manchester, Manchester, United Kingdom (Y.E., J.B., A.R.-H.); and Simcyp Limited (a Certara Company) Sheffield, United Kingdom (A.R.-H.).
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Abstract

Most of the pharmacokinetic studies conducted to calculate pediatric drug doses are based on scaling from adult data using various allometric parameters related to body size. However, these uniform scaling methods cannot account for all physiologic changes occurring during maturation, which influence various drugs in different ways. The ontogeny of physiologic and biologic functions accompanying the progression from infancy to childhood to adulthood does not proceed in a simple monotonic rate with body size for various elimination pathways. The transporters and their interplay with enzymes have a substantial role in drug metabolism and disposition. Although much is known about enzymes and their ontogeny, there is a scarcity of information on the ontogenic profile of drug transporters, particularly during the early years of human life. These ontogeny data are required for the enhancement of physiologically based pharmacokinetic models, and consequently for the prediction of pharmacokinetic profiles of new therapeutic compounds in pediatric populations. This review points to the relative ontogeny rate for enzymes and transporters and how these may confound our understanding of the role that transporters may or may not play in childhood compared with adulthood.

Footnotes

    • Received October 13, 2015.
    • Accepted December 23, 2015.
  • dx.doi.org/10.1124/dmd.115.067801.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 44 (7)
Drug Metabolism and Disposition
Vol. 44, Issue 7
1 Jul 2016
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Research ArticleSpecial Section on Pediatric Drug Disposition and Pharmacokinetics—Minireview

Age-Dependent Hepatic Drug Transport in Pediatrics

Yasmine Elmorsi, Jill Barber and Amin Rostami-Hodjegan
Drug Metabolism and Disposition July 1, 2016, 44 (7) 992-998; DOI: https://doi.org/10.1124/dmd.115.067801

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Research ArticleSpecial Section on Pediatric Drug Disposition and Pharmacokinetics—Minireview

Age-Dependent Hepatic Drug Transport in Pediatrics

Yasmine Elmorsi, Jill Barber and Amin Rostami-Hodjegan
Drug Metabolism and Disposition July 1, 2016, 44 (7) 992-998; DOI: https://doi.org/10.1124/dmd.115.067801
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