Transport studies with 5-aminosalicylate

Area of Science:

• Pharmacology
• Gastroenterology
• Drug Transport

Background:

• 5-aminosalicylate (5-ASA; mesalamine) is a key therapy for inflammatory bowel disease.
• Its therapeutic action is believed to originate from the intestinal lumen.
• Transporter-mediated secretion back to the lumen is hypothesized to maintain mucosal concentrations.

Purpose of the Study:

• To test if 5-ASA is a substrate of P-glycoprotein (P-gp) or multidrug resistance-associated protein 2 (MRP2).
• To investigate the role of these transporters in potential variable therapeutic effects of 5-ASA.
• To explore the influence of 5-ASA on the transport of other drugs, like digoxin.

Main Methods:

• Utilized polarized Caco-2 and L-MDR cell monolayers expressing P-gp.
• Employed MDCK cells transfected with human MRP2.
• Assessed basal-to-apical transport of [(3)H]5-ASA and digoxin transport in the presence of 5-ASA.

Main Results:

• P-glycoprotein-mediated efflux of 5-ASA was excluded in Caco-2 cells.
• No significant transport differences for 5-ASA were observed in L-MDR1 and MRP2 cells.
• 5-ASA did not affect the transport of digoxin in Caco-2 cells.

Conclusions:

• Intestinal secretion of 5-ASA is not mediated by P-gp or MRP2.
• These findings exclude common efflux transporters in 5-ASA intestinal secretion.
• Further research is required to identify the specific active carrier systems involved in 5-ASA transport.