Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

Miriam Mooij, AT Nies, CAJ Knibbe, E Schaeffeler, Dick Tibboel, M Schwab, Saskia de Wildt

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Abstract

Membrane transporters play an essential role in the transport of endogenous and exogenous compounds, and consequently they mediate the uptake, distribution, and excretion of many drugs. The clinical relevance of transporters in drug disposition and their effect in adults have been shown in drug-drug interaction and pharmacogenomic studies. Little is known, however, about the ontogeny of human membrane transporters and their roles in pediatric pharmacotherapy. As they are involved in the transport of endogenous substrates, growth and development may be important determinants of their expression and activity. This review presents an overview of our current knowledge on human membrane transporters in pediatric drug disposition and effect. Existing pharmacokinetic and pharmacogenetic data on membrane substrate drugs frequently used in children are presented and related, where possible, to existing ex vivo data, providing a basis for developmental patterns for individual human membrane transporters. As data for individual transporters are currently still scarce, there is a striking information gap regarding the role of human membrane transporters in drug therapy in children.
Original languageUndefined/Unknown
Pages (from-to)507-524
Number of pages18
JournalClinical Pharmacokinetics
Volume55
Issue number5
DOIs
Publication statusPublished - 2016

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