Intestinal Absorption of Drugs Mediated by Drug Transporters: Mechanisms and Regulation

doi:10.2133/dmpk.18.1

Drug Metabolism and Pharmacokinetics

Volume 18, Issue 1, 2003, Pages 1-15

https://doi.org/10.2133/dmpk.18.1 Get rights and content

Summary:

The absorption of drugs from the gastrointestinal tract is one of the important determinants for oral bioavailability. Development of in vitro experimental techniques such as isolated membrane vesicles and cell culture systems has allowed us to elucidate the transport mechanisms of various drugs across the plasma membrane. Recent introduction of molecular biological techniques resulted in the successful identification of drug transporters responsible for the intestinal absorption of a wide variety of drugs. Each transporter exhibits its own substrate specificity, though it usually shows broad substrate specificity. In this review, we first summarize the recent advances in the characterization of drug transporters in the small intestine, classified into peptide transporters, organic cation transporters and organic anion transporters. In particular, peptide transporter (PEPT1) is the best-characterized drug transporter in the small intestine, and therefore its utilization to improve the oral absorption of poorly absorbed drugs is briefly described. In addition, regulation of the activity and expression levels of drug transporters seems to be an important aspect, because alterations in the functional characteristics and/or expression levels of drug transporters in the small intestine could be responsible for the intra- and interindividual variability of oral bioavailability of drugs. As an example, regulation of the activity and expression of PEPT1 is summarized.

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ReviewIntestinal Absorption of Drugs Mediated by Drug Transporters: Mechanisms and Regulation

Summary:

J. Biol. Chem.

Methods Enzymol.

Gastroenterology

Adv. Drug Deliv. Rev.

Methods Enzymol.

Kidney Int.

J. Pharm. Sci.

Eur. J. Pharm. Sci.

J. Pharm. Sci.

J. Control. Release

Drug Metabol. Pharmacokin.

Drug Metabol. Pharmacokin.

J. Biol. Chem.

Biochim. Biophys. Acta

J. Nutr.

J. Nutr.

Gastroenterology

J. Control. Release

Trends Pharmacol. Sci.

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Bioorg. Med. Chem.

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J. Biol. Chem.

Biochem. Biophys. Res. Commun.

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Biochem. Biophys. Res. Commun.

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Cell

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Biochem. Biophys. Res. Commun.

Gastroenterology

Eur. J. Pharm. Sci.

Adv. Drug Deliv. Rev.

Trends Pharmacol. Sci.

Biochem. Biophys. Res. Commun.

Organic cation transport in the renal brush-border and basolateral membranes

Transepithelial transport of oral cephalosporins by monolayers of intestinal epithelial cell line Caco-2: specific transport systems in apical and basolateral membranes

J. Pharmacol. Exp. Ther.

Intestinal drug absorption and metabolism in cell culture: Caco-2 and beyond

Pharm. Res.

Human intestinal permeability

J. Pharm. Sci.

Expression cloning and cDNA sequencing of the Na+/glucose co-transporter

Nature

Expression cloning of a mammalian proton-coupled oligopeptide transporter

Nature

Drug excretion mediated by a new prototype of polyspecific transporter

Nature

Expression cloning of a rat liver Na+-independent organic anion transporter

Proc. Natl. Acad. Sci. USA

Cellular and molecular mechanisms of renal tubular secretion of organic anions and cations

Clin. Exper. Nephrol.

Structure of renal organic anion and cation transporters

Am. J. Physiol. Renal Physiol.

The multispecific organic anion transporter (OAT) family

Pflügers Arch.

The organic anion transporter family: from physiology to ontogeny and the clinic

Am. J. Physiol. Renal Physiol.

Molecular aspects of renal anionic drug transport

Annu. Rev. Physiol.

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Annu. Rev. Physiol.

Review
Intestinal Absorption of Drugs Mediated by Drug Transporters: Mechanisms and Regulation

Expression cloning and cDNA sequencing of the Na⁺/glucose co-transporter

Expression cloning of a rat liver Na⁺-independent organic anion transporter