5-Aminosalicylic acid concentration in mucosal interstitium of cat small and large intestine.

Uncertainty regarding the concentration of 5-ASA within the mucosal interstitium has been a major limitation of defining the protective mechanisms of 5-ASA in intestinal inflammation. Therefore, we measured the concentration of 5-ASA in intestinal lymph and venous plasma during luminal perfusion of the cat small and large intestine with 10 mM 5-ASA. Blood and lymph flows were measured in each segment. 5-ASA and N-acetyl-5-ASA were extracted from plasma and lymph and quantified using fluorescence spectroscopy. Luminal perfusion of the terminal ileum with 5-ASA resulted in the following concentration profile: intestinal venous plasma (143 +/- 30 micrograms/ml) much greater than lymph (43 +/- 17 micrograms/ml) = systemic arterial plasma (40 +/- 11 micrograms/ml). In the colon the local venous plasma concentration of 5-ASA was 20 +/- 6 micrograms/ml compared to 2.0 +/- 1.0 micrograms/ml in systemic arterial plasma. N-Acetyl-5-ASA was found to comprise less than 5% of the total metabolite concentration in both ileum and colon. We also found that 58% of luminal 5-ASA was absorbed per minute in the terminal ileum, whereas only 3%/min was absorbed from the colon. The results of this study suggest that: (1) the mucosal interstitial concentration of 5-ASA in the terminal ileum and colon are approximately 100 micrograms/ml (654 microM) and 20 micrograms/ml (164 microM), respectively; and (2) the rate of 5-ASA absorption in the terminal ileum is approximately seven times greater than that in the colon.