Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 May;55(5):507-24.
doi: 10.1007/s40262-015-0328-5.

Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

Miriam G Mooij  1 , Anne T Nies  2   3 , Catherijne A J Knibbe  4   5 , Elke Schaeffeler  2   3 , Dick Tibboel  1 , Matthias Schwab  2   6 , Saskia N de Wildt  7
Affiliations
Review

Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics

Miriam G Mooij et al. Clin Pharmacokinet. 2016 May.

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Suggested ontogeny of ABCB1 expression in intestine, liver, kidney, and brain. ABC adenosine triphosphate (ATP)-binding cassette
Fig. 2
Fig. 2
Membrane transporters and their relationship with commonly prescribed drugs to children: digoxin, tacrolimus, morphine, pravastatin, and atorvastatin. ABC adenosine triphosphate (ATP)-binding cassette, CYP cytochrome P450, OATP organic anion-transporting polypeptide, OCT organic cation transporter, UGT uridine 5′-diphospho-glucuronosyltransferase
See this image and copyright information in PMC

References

    1. International Transporter Consortium. Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010;9(3):215–236. doi: 10.1038/nrd3028. - DOI - PMC - PubMed
    1. Kell DB, Dobson PD, Oliver SG. Pharmaceutical drug transport: the issues and the implications that it is essentially carrier-mediated only. Drug Discov Today. 2011;16(15–16):704–714. doi: 10.1016/j.drudis.2011.05.010. - DOI - PubMed
    1. Moitra K, Dean M. Evolution of ABC transporters by gene duplication and their role in human disease. Biol Chem. 2011;392(1–2):29–37. - PubMed
    1. Hediger MA, Clemencon B, Burrier RE, Bruford EA. The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol Aspects Med. 2013;34(2–3):95–107. doi: 10.1016/j.mam.2012.12.009. - DOI - PMC - PubMed
    1. DeGorter MK, Xia CQ, Yang JJ, Kim RB. Drug transporters in drug efficacy and toxicity. Annu Rev Pharmacol Toxicol. 2012;52:249–273. doi: 10.1146/annurev-pharmtox-010611-134529. - DOI - PubMed

Publication types

Substances

LinkOut - more resources