Disposition of Mesalazine from Mesalazine-Delivering Drugs in Patients with Inflammatory Bowel Disease, with and without Diarrhoea

Abstract

The disposition of mesalazine from the azo compounds sulphasalazine and olsalazine (Dipentum) and from the slow-release mesalazine drugs Pentasa, Asacol, and Salofalk was studied in 20 patients with inflammatory bowel disease. Ten of them had diarrhoea, and 10 had normal stools. On the last 2 days of a 7-day maintenance treatment with each of the study drugs urine and faeces were collected for determination of mesalazine, acetyl-mesalazine, and unsplit azo compound. In patients with and without diarrhoea the urinary and the faecal excretion of acetyl-mesalazine was lowest during treatment with olsalazine. The proportion of acetyl-mesalazine in faeces was highest during treatment with Pentasa in both groups. The presence of diarrhoea was associated with a decrease in the proportion of acetyl-mesalazine in faeces during treatment with all drugs, not significant only for Pentasa. The proportion of unsplit azo compound in faeces increased in the case of diarrhoea to almost 50%. It is concluded that in patients with inflammatory bowel disease diarrhoea substantially influences the disposition from all these drugs except Pentasa.

Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs

“…The azo formulations sulphasalazine and olsalazine were less completely split in patients with diarrhoea than in those without diarrhoea 49. Release of 5-ASA from Asacol in patients with diarrhoea was characterised by a high proportion of 5-ASA in stools but little in the acetylated form, indicating release primarily in the distal colon 49.…”

“…For each formulation, serum and urine concentrations of the metabolite N -acetyl-5-ASA are greater than those of 5-ASA 49. A high urinary excretion of N -acetyl-5-ASA indicates early release of 5-ASA from the formulation in the proximal gastrointestinal tract 49.…”

“…A high urinary excretion of N -acetyl-5-ASA indicates early release of 5-ASA from the formulation in the proximal gastrointestinal tract 49. Recovery of N -acetyl-5-ASA in the faeces indicates timely release of 5-ASA in the colonic lumen with its subsequent mucosal absorption, metabolism to N -acetyl-5-ASA, and release of the latter back into the lumen.…”

Biological Variability and Targeted Delivery of Therapeutics for Inflammatory Bowel Diseases: An In Silico Approach

“…It is known that metabolism of the active component (5-ASA) occurs in the gut [26][27][28] and the metabolite is secreted back to the lumen and eventually excreted without being absorbed [29,30]. Hence, the total fecal recovery includes the metabolized drug in the intestine and the amount of drug released in the colon.…”

Update on the role of modified release mesalamine in the management of ulcerative colitis and Crohn’s disease

“…6 The pharmacokinetics of delayed release mesalamines do not appear altered by the use of acid suppressants 7 and are not altered significantly in patients with diarrhea. 8 …”