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

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Abstract
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 μg/ml) ≫ lymph (43 ±17 μg/ml)=systemic arterial plasma (40±11 μg/ml). In the colon the local venous plasma concentration of 5-ASA was 20±6 μg/ml compared to 2.0±1.0 μg/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 μg/ml (654 μM) and 20 μg/ml (164 μM), respectively; and (2) the rate of 5-ASA absorption in the terminal ileum is approximately seven times greater than that in the colon.