Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion

Sulfasalazine is a drug that is chemically related to aspirin and used in the treatment of ulcerative colitis. Oral sulfasalazine is broken down into two metabolites in the lower digestive tract. Of these, 5-aminosalicylic acid (5-ASA) is the therapeutically active product. Since the discovery that 5-ASA (which by itself is not orally active) is the active molecule, a variety of drug delivery strategies have been developed to chemically link 5-ASA with other molecules, and coated capsules and slow-release formulations have been designed to get the 5-ASA into the large intestine where it acts on the luminal side of the colon (inside the digestive tract). Intestinal absorption of 5-ASA occurs, but increased blood levels of the drug do not confer any additional therapeutic benefit and may, in fact, be toxic to the kidney. Fourteen patients with ulcerative colitis in remission took part in a study to evaluate the ability of several different formulations of 5-ASA-containing preparations to increase colonic concentrations of the drug. Each subject received a novel formulation (olsalazine; disodium azodisalicylate), both as coated tablets and gel capsules, and three other commercially available mesalazine formulations (Asacol, Pentasa, or Salofalk). Colonic and blood levels, as well as urinary excretion, of 5-ASA were determined after five days of each treatment. Olsalazine treatment doubled the colonic concentration of 5-ASA compared with Pentasa and Salofalk but not with Asacol; blood levels and urinary excretion of 5-ASA were decreased compared with the mesalazines. This indicates that olsalazine is one of the best vehicles for delivering 5-ASA to its site of action, while reducing the systemic concentrations of the drug that may be harmful to the kidney. (Consumer Summary produced by Reliance Medical Information, Inc.)