Olsalazine

Olsalazine and its metabolite olsalazine-S, are more than 99% bound to plasma proteins. Less than 1% of both olsalazine and olsalazine-S appears undissociated in plasma. It does not interfere with the protein binding of warfarin. Mesalamine (5-aminosalicylic acid, 5-ASA) and its metabolite, N-acetyl-5-ASA, are 74 and 81%, respectively, bound to plasma proteins.

Olsalazine is an anti-inflammatory agent that blocks the production of cyclooxygenase (COX)-derived products of arachidonic acid metabolism. It works to alleviate inflammation in ulcerative colitis. Olsalazine was shown to decrease water and sodium absorption. While olsalazine is not expected to affect the motility and transit time of small intestines, it decreased small bowel transit time at high doses ranging from 60 to 120 mg/kg. In about 40% of the patients with ulcerative colitis, administration of olsalazine 1g daily was associated with a decrease in whole gut transit time.

Upon administration, the azo bond connecting two molecules of mesalamine (also known as 5-aminosalicylic acid or 5-ASA) is cleaved by azoreductase-containing bacteria in the colon. The two molecules of mesalamine are released to mediate therapeutic effects. The exact mechanism of action of olsalazine and its active moiety mesalamine in ulcerative colitis has not been elucidated; however, it is understood that mesalamine mediates an anti-inflammatory action on epithelial cells of the colon. The COX-derived (i.e., prostanoids such as prostaglandin E2) and lipoxygenase-derived products (i.e., leukotrienes [LTs] and hydroxyeicosatetraenoic acids [HETEs]) of arachidonic acid metabolism have been implicated in the pathogenesis and maintenance of inflammatory disorders, including ulcerative colitis and inflammatory bowel disease. Mesalamine may attenuate inflammation by blocking the COX enzyme and inhibiting prostaglandin production in the colon. Olsalazine was also shown to inhibit xanthine oxidase, an enzyme that generates oxygen-derived free radicals. Olsalazine may attenuate intestinal inflammation by limiting macrophage migration to inflamed intestinal mucosa: it was shown to inhibit _in vitro_ migration of intestinal macrophages in response to leukotriene B₄. Olsalazine may also act as a free radical scavenger, and mesalazine may suppress fatty acid peroxidation.