Luminal concentrations of orally ingested 4-aminosalicylic acid as determined by in-vivo equilibrium dialysis

We measured 4-aminosalicylic acid (4-ASA) levels in faecal water by in-vivo equilibrium dialysis during oral ingestion of drug by two different dose protocols (A and B). In Protocol A, 5 normal subjects ingested 3 g of 4-ASA as the free acid and 20 mg of metaclopromide per day. On Day 5, small dialysis sacs filled with dextran 40 were ingested and the oral drug was continued until the sacs were retrieved from the stool. Protocol B followed the same format except that 3 g of 4-ASA was ingested twice daily and metaclopromide was omitted. In both protocols concentrations of 4-ASA and N-acetylated 4-ASA in sac contents were measured by HPLC. In-vitro dialysis studies showed bi-directional equilibrium was reached within 120 min. During Protocol A, intraluminal concentrations of total 4-ASA ranged from 14.0 to 32.2 mmol/L with a mean of 20.6 mmol/L. With Protocol B, total 4-ASA levels ranged from 20.1 to 41.3 mmol/L with a mean of 33.9 mmol/L. From 90 to 99% of the drug in the dialysates was N-acetylated. These concentrations of total 4-ASA are similar to those of 5-ASA after ingestion of therapeutic doses of sulphasalazine or absorption-resistant formulations of 5-ASA. Thus, oral 4-ASA could have a role in the treatment of inflammatory bowel disease.