J Clin Pharmacol
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First published on October 16, 2009
The Journal of Clinical Pharmacology 2009, doi:10.1177/0091270009343696
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©© 2009 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology, 10.1177/0091270009343696

Article

Influence of Development, HIV Infection, and Antiretroviral Therapies on the Gene Expression Profiles of ABC Transporters in Human Lymphocytes

Carole Giraud *, Sandra Manceau 1, Xavier Declèves 2, François Goffinet 1, Jean-Pierre Morini 3, Hélène Chappuy 4, Frédéric Batteux 2, Sandrine Chouzenoux 2, Salah Yousif 2, Jean-Michel Scherrmann 2, Stéphane Blanche 4, and Jean-Marc Tréluyer 1

1 Hôpital Cochin and Université Paris Descartes
2 Université Paris Descartes
3 Hôpital Cochin
4 Hôpital Necker Enfants Malades and Université Paris Descartes

* To whom correspondence should be addressed. E-mail: carole.giraud{at}cch.aphp.fr.


  Abstract
The efficacy of drugs acting on lymphocytes like anticancer, immunosuppressive, and antiretroviral drugs depends on their intracellular concentrations, which could be modulated by membrane efflux pumps belonging to the ABC transporter superfamily. The gene expression profiles of 6 main ABC transporters (MDR1, MRP1, MRP3, MRP4, MRP5, and BCRP) were established in lymphocytes from birth to adulthood using blood samples from 57 children and 15 adults (34 and 5 HIV-infected, respectively). Gene expression levels were quantified by quantitative RT-PCR. In adults, the MRP1 gene had the highest expression, followed by the MRP5 gene. BCRP and MRP4 genes were significantly higher expressed at birth than after 1 month of life. Neither HIV infection nor antiretroviral therapies modulated the gene expression profiles of ABC transporters. In conclusion, drugs that are substrates of BCRP and MRP4, like zidovudine, may have an altered efficacy in newborns.
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