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PepT1, ASBT-Linked Prodrug Strategy to Improve Oral Bioavailability and Tissue Targeting Distribution

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With the rapid development of molecular biology, various of drug transporters have been discovered in several important organs of the body, which determine intracellular exposure and pharmacokinetic performances of drugs by modulating cellular entry and exit. This article focuses on the design of transporter-linked prodrug to enhance oral bioavailability and to acquire tissue-specific distribution pattern, especially paying attention to peptide transporter 1 (PepT1) and apical sodium dependent bile acid transporter (ASBT). Conjugation of the native promotety to active drug was one of the effective methods to improve membrane permeability and distribution profiles of drugs. In this review, we highlight the transporter-linked prodrug design modality based on PepT1 and ASBT. The biology of transporters, structure-transport relationship, key features of natural substrates and successful examples of transporter-linked prodrugs are overviewed in detail.
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Keywords: ASBT; PepT1; oral bioavailability; prodrug; tissue targeting

Document Type: Research Article

Publication date: January 1, 2015

More about this publication?
  • 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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