title: Biopharmaceutical evaluation of salicylazosulfanilic acid as a novel colon-targeted prodrug of 5-aminosalicylic acid.
abstract: A prodrug of 5-aminosalicylic acid (5-ASA), salicylazosulfanilic acid (SASA), which consists of sulfanilic acid linked to 5-ASA through an azo-linkage was newly synthesized. Biopharmaceutical properties of SASA were evaluated in comparison with those of salicylazosulfapyridine (SASP) in rats. Since SASA is much more hydrophilic than SASP, the absorption of SASA from the small intestine was less in comparison with SASP. When SASA and SASP were incubated with the rat intestinal contents under anaerobic conditions, both compounds were stable in the small-intestinal contents, but were rapidly degraded to 5-ASA in the cecal and the colonic contents. The degradation to 5-ASA by the large-intestinal contents was suppressed by the pretreatment with kanamycin sulfate, suggesting that the bioconversion of SASA is mediated by the intestinal microflora similarly to that of SASP and that SASA is also a prodrug of 5-ASA. After the oral administration, 5-ASA was found neither in the stomach nor in the small intestine in case of both prodrugs. Most of the prodrugs were transferred to the lower intestine where they were degraded to 5-ASA. The recovery of SASA including the metabolites from the gastrointestinal tract at four hours after the oral administration was significantly greater than that of SASP. Accordingly, SASA is free from the liberation of sulfapyridine, the adverse effect moiety of SASP, and less absorbable in the small intestine. Thus, the beneficial characteristics of SASA as an excellent colon-targeted prodrug of 5-ASA were clarified.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kurosaki
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: T
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000284:Administration, Oral; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001702:Biopharmaceutics; D001711:Biotransformation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003106:Colon / Q000378:metabolism*; D015195:Drug Design; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008297:Male; D019804:Mesalamine; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013425:Sulfanilic Acids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D012460:Sulfasalazine / Q000493:pharmacokinetics
chemical_list: D000636:Aminosalicylic Acids; D011355:Prodrugs; D013425:Sulfanilic Acids; D012460:Sulfasalazine; D019804:Mesalamine