Drug Transporters in the Intestine

Bente Steffansen

Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

Abstract

The enterocyte monolayer in the intestinal membrane impacts on the bioavailability (BA) of many orally administered active pharmaceutical ingredients (APIs). The monolayer expresses a multitude of membrane transporters belonging to the solute carrier (SLC) and ATP-binding cassette (ABC) families that may impact drug absorption. Thus absorptive transporters may facilitate BA of APIs that are substrates/victims for the transporters and have permeability-limited absorption, i.e. those that are classified in the biopharmaceutics classification system (BCS) Class 3 and 4. On the other hand, exsorptive transporters may restrict BA of APIs that are victims for these efflux transporters, especially those APIs classified to have solubility-limited absorption, i.e. compounds in BCS Class 2 and 4. The aim of the present Chapter is to review drug transporters (DTs) present within the intestine and to discuss and exemplify their roles in drug absorption/exsorption and in drug-drug interactions (DDIs). Although focus in the present Chapter is on DTs that are mentioned in American and European regulatory guidances, the intestinal transporters for nutrients and endogens (endogenous compounds) are also briefly considered, since some nutrient transporters (NTs) are also DTs. An example of a NT, which is also a DT is the peptide transporter 1 (PEPT1)/ SLC15A1. Thus absorption of di/tri-peptides rely on this transporter as do several APIs such as cefadroxile. Many APIs are substrates and/or inhibitors to the intestinal exsorptive DTs. An example is the API sulfasalazine, which is a substrate for breast cancer resistance protein (BCRP)/ABCG2. Sulfasalazine absorption is found to increase when human volunteers are administered high concentrations together with the inhibitor and spice curcumin. In conclusion, to date 51 intestinal transporters have been identified of which 14 are known to play a role in drug BA.
Original languageEnglish
Title of host publicationDrug Transporters : Role and Importance in ADME and Drug Development Complete Set
EditorsGlynis Nicholls, Kuresh Youdim
PublisherRoyal Society of Chemistry
Publication date2016
ISBN (Print)978-1782620693
Publication statusPublished - 2016
SeriesRSC Drug Discovery Series
ISSN2041-3203

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Intestines
Pharmaceutical Preparations
Sulfasalazine
Food
Spices
Curcumin
Enterocytes
Drug Interactions
Volunteers

Cite this

Steffansen, B. (2016). Drug Transporters in the Intestine. In G. Nicholls, & K. Youdim (Eds.), Drug Transporters: Role and Importance in ADME and Drug Development Complete Set Royal Society of Chemistry. RSC Drug Discovery Series
Steffansen, Bente. / Drug Transporters in the Intestine. Drug Transporters: Role and Importance in ADME and Drug Development Complete Set. editor / Glynis Nicholls ; Kuresh Youdim. Royal Society of Chemistry, 2016. (RSC Drug Discovery Series).
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Steffansen, B 2016, Drug Transporters in the Intestine. in G Nicholls & K Youdim (eds), Drug Transporters: Role and Importance in ADME and Drug Development Complete Set. Royal Society of Chemistry, RSC Drug Discovery Series.

Drug Transporters in the Intestine. / Steffansen, Bente.

Drug Transporters: Role and Importance in ADME and Drug Development Complete Set. ed. / Glynis Nicholls; Kuresh Youdim. Royal Society of Chemistry, 2016.

Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

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N2 - The enterocyte monolayer in the intestinal membrane impacts on the bioavailability (BA) of many orally administered active pharmaceutical ingredients (APIs). The monolayer expresses a multitude of membrane transporters belonging to the solute carrier (SLC) and ATP-binding cassette (ABC) families that may impact drug absorption. Thus absorptive transporters may facilitate BA of APIs that are substrates/victims for the transporters and have permeability-limited absorption, i.e. those that are classified in the biopharmaceutics classification system (BCS) Class 3 and 4. On the other hand, exsorptive transporters may restrict BA of APIs that are victims for these efflux transporters, especially those APIs classified to have solubility-limited absorption, i.e. compounds in BCS Class 2 and 4. The aim of the present Chapter is to review drug transporters (DTs) present within the intestine and to discuss and exemplify their roles in drug absorption/exsorption and in drug-drug interactions (DDIs). Although focus in the present Chapter is on DTs that are mentioned in American and European regulatory guidances, the intestinal transporters for nutrients and endogens (endogenous compounds) are also briefly considered, since some nutrient transporters (NTs) are also DTs. An example of a NT, which is also a DT is the peptide transporter 1 (PEPT1)/ SLC15A1. Thus absorption of di/tri-peptides rely on this transporter as do several APIs such as cefadroxile. Many APIs are substrates and/or inhibitors to the intestinal exsorptive DTs. An example is the API sulfasalazine, which is a substrate for breast cancer resistance protein (BCRP)/ABCG2. Sulfasalazine absorption is found to increase when human volunteers are administered high concentrations together with the inhibitor and spice curcumin. In conclusion, to date 51 intestinal transporters have been identified of which 14 are known to play a role in drug BA.

AB - The enterocyte monolayer in the intestinal membrane impacts on the bioavailability (BA) of many orally administered active pharmaceutical ingredients (APIs). The monolayer expresses a multitude of membrane transporters belonging to the solute carrier (SLC) and ATP-binding cassette (ABC) families that may impact drug absorption. Thus absorptive transporters may facilitate BA of APIs that are substrates/victims for the transporters and have permeability-limited absorption, i.e. those that are classified in the biopharmaceutics classification system (BCS) Class 3 and 4. On the other hand, exsorptive transporters may restrict BA of APIs that are victims for these efflux transporters, especially those APIs classified to have solubility-limited absorption, i.e. compounds in BCS Class 2 and 4. The aim of the present Chapter is to review drug transporters (DTs) present within the intestine and to discuss and exemplify their roles in drug absorption/exsorption and in drug-drug interactions (DDIs). Although focus in the present Chapter is on DTs that are mentioned in American and European regulatory guidances, the intestinal transporters for nutrients and endogens (endogenous compounds) are also briefly considered, since some nutrient transporters (NTs) are also DTs. An example of a NT, which is also a DT is the peptide transporter 1 (PEPT1)/ SLC15A1. Thus absorption of di/tri-peptides rely on this transporter as do several APIs such as cefadroxile. Many APIs are substrates and/or inhibitors to the intestinal exsorptive DTs. An example is the API sulfasalazine, which is a substrate for breast cancer resistance protein (BCRP)/ABCG2. Sulfasalazine absorption is found to increase when human volunteers are administered high concentrations together with the inhibitor and spice curcumin. In conclusion, to date 51 intestinal transporters have been identified of which 14 are known to play a role in drug BA.

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Steffansen B. Drug Transporters in the Intestine. In Nicholls G, Youdim K, editors, Drug Transporters: Role and Importance in ADME and Drug Development Complete Set. Royal Society of Chemistry. 2016. (RSC Drug Discovery Series).