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(Section A: Molecular, Structural, and Cellular Biology of Drug Transporters) Peptide Transporters: Structure, Function, Regulation and Application for Drug Delivery

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Proton-coupled peptide transporters, localized at brush-border membranes of intestinal and renal epithelial cells, play important roles in protein absorption and the conservation of peptide-bound amino nitrogen. These transporters also have significant pharmacological and pharmacokinetic relevance to the transport of various peptide-like drugs such as β-lactam antibiotics. The identification and molecular characterization of H+ / peptide cotransporters (PEPT1 and PEPT2) have facilitated the clarification of many aspects of these transporters such as the structure / function relationship and regulation. Recent findings that intestinal PEPT1 can transport L-valine ester prodrugs such as valacyclovir provided a major step forward toward the development of novel drug delivery systems. It has been demonstrated that peptide transporters, which have a similar substrate specificity to PEPT1 and PEPT2, but possess other distinct functional properties, are localized at basolateral membranes of intestinal and renal epithelial cells. This review highlights the recent advances in our knowledge of the cellular and molecular nature of PEPT1, PEPT2 and the basolateral peptide transporters.
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Keywords: lactam antibiotics; peptide-bound amino nitrogen; valacyclovir

Document Type: Review Article

Affiliations: Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.

Publication date: February 1, 2004

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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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