Abstract
Although oral drug administration is currently the favorable route of administration, intestinal drug absorption is challenged by several highly variable and poorly predictable processes such as gastrointestinal motility, intestinal drug solubility and intestinal metabolism. One further determinant identified and characterized during the last two decades is the intestinal drug transport that is mediated by several transmembrane proteins such as P-gp, BCRP, PEPT1 and OATP2B1. It is well-established that intestinal transporters can affect oral absorption of many drugs in a significant manner either by facilitating their cellular uptake or by pumping them back to gut lumen, which limits their oral bioavailability. Their functional relevance becomes even more apparent in cases of unwanted drug-drug interactions when concomitantly given drugs that cause transporter induction or inhibition, which in turn leads to increased or decreased drug exposure. The longitudinal expression of several intestinal transporters is not homogeneous along the human intestine, which may have functional implications on the preferable site of intestinal drug absorption. Besides the knowledge about the expression of pharmacologically relevant transporters in human intestinal tissue, their exact localization on the apical or basolateral membrane of enterocytes is also of interest but in several cases debatable. Finally, there is obviously a coordinative interplay of intestinal transporters (apical–basolateral), intestinal enzymes and transporters as well as intestinal and hepatic transporters. This review aims to give an updated overview about the expression, localization, regulation and function of clinically relevant transporter proteins in the human intestine.
Acknowledgments
This study was supported by the German Federal Ministry for Education and Research (Grant no. 03IPT612X, InnoProfile-Transfer).
Conflict of interest statement: All other authors declare no conflict of interest.
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©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: the transporter colloquium – spotlight on membrane proteins
- HIGHLIGHT: 10. TRANSPORT-COLLOQUIUM OF THE GBM STUDY SECTION ‘BIOMEMBRANES’
- Transmitting the energy: interdomain cross-talk in Pdr5
- Stoichiometry determination of macromolecular membrane protein complexes
- The novel class of seven transmembrane segment inverted repeat carriers
- Expression, regulation and function of intestinal drug transporters: an update
- Guardians in a stressful world: the Opu family of compatible solute transporters from Bacillus subtilis
- Control of membrane fluidity: the OLE pathway in focus
- Biophysical methods toolbox to study ABC exporter structure and function
- Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families
- Strong pH dependence of coupling efficiency of the Na+ – translocating NADH:quinone oxidoreductase (Na+-NQR) of Vibrio cholerae
- Review
- Glutathione and glutathione derivatives in immunotherapy
- Research Articles/Short Communications
- Molecular Medicine
- E-beam crosslinked nanogels conjugated with monoclonal antibodies in targeting strategies
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: the transporter colloquium – spotlight on membrane proteins
- HIGHLIGHT: 10. TRANSPORT-COLLOQUIUM OF THE GBM STUDY SECTION ‘BIOMEMBRANES’
- Transmitting the energy: interdomain cross-talk in Pdr5
- Stoichiometry determination of macromolecular membrane protein complexes
- The novel class of seven transmembrane segment inverted repeat carriers
- Expression, regulation and function of intestinal drug transporters: an update
- Guardians in a stressful world: the Opu family of compatible solute transporters from Bacillus subtilis
- Control of membrane fluidity: the OLE pathway in focus
- Biophysical methods toolbox to study ABC exporter structure and function
- Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families
- Strong pH dependence of coupling efficiency of the Na+ – translocating NADH:quinone oxidoreductase (Na+-NQR) of Vibrio cholerae
- Review
- Glutathione and glutathione derivatives in immunotherapy
- Research Articles/Short Communications
- Molecular Medicine
- E-beam crosslinked nanogels conjugated with monoclonal antibodies in targeting strategies