A new slow-release form of 5-aminosalicylic acid for the oral treatment of inflammatory bowel disease. Biopharmaceutic and clinical pharmacokinetic characteristics

Abstract

A new enteric coated form of 5-aminosalicylic acid (5-AS, Salofalk) for the treatment of inflammatory bowel disease was developed. In 11 hospitalized patients with Crohn's disease or ulcerative colitis the steady-state pharmacokinetics of 5-AS and its major metabolite, N-acetyl-5-AS (Ac-5-AS), was investigated. During treatment with 0.5 g 5-AS tid elimination half-life (t 1/2) ranged from 0.7 to 2.4 h (1.4 +/- 0.6 h, mean +/- SD; n = 6) and mean steady-state plasma levels (Css) of 5-AS and Ac-5-AS averaged 0.7 +/- 0.4 micrograms/ml and 1.2 +/- 0.3 micrograms/ml, respectively. Treatment with the smaller dose of 0.25 g 5-AS tid (n = 5) resulted in a shorter t 1/2 (0.6 +/- 0.2 h), lower Css for 5-AS (0.4 +/- 0.2 micrograms/ml) and Ac-5-AS (1.0 +/- 0.2 micrograms/ml). Urinary and fecal recovery of total 5-AS was calculated to 44 +/- 21% and 35 +/- 10%, respectively. Both compounds were slightly bound to plasma proteins (5-AS: 43%, Ac-5-AS: 78%). In conclusion, the present data would suggest that the new oral dosage form delivers sufficient amounts of therapeutically active 5-AS for local and systemic action in patients with inflammatory bowel disease.