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Clin Pharmacol Ther. 2013 Jul;94(1):52-63. doi: 10.1038/clpt.2013.74. Epub 2013 Apr 8.

Emerging transporters of clinical importance: an update from the International Transporter Consortium.

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1
Drug Disposition, Lilly Research Laboratories, Indianapolis, Indiana, USA. k_hillgren@lilly.com

Abstract

The International Transporter Consortium (ITC) has recently described seven transporters of particular relevance to drug development. Based on the second ITC transporter workshop in 2012, we have identified additional transporters of emerging importance in pharmacokinetics, interference of drugs with transport of endogenous compounds, and drug-drug interactions (DDIs) in humans. The multidrug and toxin extrusion proteins (MATEs, gene symbol SLC47A) mediate excretion of organic cations into bile and urine. MATEs are important in renal DDIs. Multidrug resistance proteins (MRPs or ABCCs) are drug and conjugate efflux pumps, and impaired activity of MRP2 results in conjugated hyperbilirubinemia. The bile salt export pump (BSEP or ABCB11) prevents accumulation of toxic bile salt concentrations in hepatocytes, and BSEP inhibition or deficiency may cause cholestasis and liver injury. In addition, examples are presented on the roles of nucleoside and peptide transporters in drug targeting and disposition.

PMID:
23588305
DOI:
10.1038/clpt.2013.74
[Indexed for MEDLINE]
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