Transport studies with 5-aminosalicylate.

Abstract

OBJECTIVE:

It is generally accepted that 5-aminosalicylate (5-ASA; mesalamine), widely used in inflammatory bowel disease therapy, exerts its action from the intraluminal site of the intestine. In addition to local metabolism of 5-ASA, it has been assumed that therapeutic mucosal concentrations of 5-ASA depend on transporter-mediated secretion back to the lumen.

METHODS:

We tested the hypothesis that 5-ASA represents a substrate of P-glycoprotein (P-gp) and/or multidrug resistance-associated protein 2 (MRP2), thereby possibly contributing to variable therapeutic effects. Polarized, basal-to-apical transport of [(3)H]5-ASA was studied in monolayers of Caco-2 and L-MDR cells, both of which express P-gp in their apical membrane, as well as in MDCK cells transfected with human MRP2. Moreover, we investigated the influence of 5-ASA on transport of digoxin in Caco-2 cells.

RESULTS:

In Caco-2 cells a P-gp-mediated efflux of 5-ASA (5-500 muM) could be excluded. Likewise, in L-MDR1 and MRP2 cells no transport differences in either the basal-to-apical or apical-to-basal direction were measurable. 5-ASA (50 muM to 5 mM) had no effect on the transport of digoxin.

CONCLUSION:

From these in-vitro experiments one can conclude that intestinal secretion of 5-ASA is apparently not mediated by P-gp or MRP2. Further studies are needed to identify the nature of the involved active carrier system(s).

• Authors: Hua-Wen Xin, Matthias Schwab, Ulrich Klotz
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 62 Issue 10 Pg. 871-5 (Oct 2006) ISSN: 0031-6970 [Print] Germany
• PMID: 16944117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCC2 protein, human
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Anti-Inflammatory Agents, Non-Steroidal
• Membrane Transport Proteins
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins
• Tritium
• Mesalamine
• Digoxin
• Inulin

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, physiology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (metabolism, pharmacokinetics, pharmacology)
• Biological Transport (drug effects)
• Caco-2 Cells
• Cell Line
• Cell Membrane Permeability (drug effects)
• Digoxin (metabolism, pharmacokinetics)
• Dose-Response Relationship, Drug
• Humans
• Inulin (metabolism, pharmacokinetics)
• LLC-PK1 Cells
• Membrane Transport Proteins (genetics, physiology)
• Mesalamine (metabolism, pharmacokinetics, pharmacology)
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins (genetics, physiology)
• Swine
• Transfection
• Tritium