Olsalazine

302.24

302.24

1312995-182-4

ULS5I8J03O

DTXSID8023391

C1176

A - Alimentary tract and metabolism

2927000090

139.78000

2.90960

1.3578 (rough estimate)

>300 °C @ Solvent: Acetic acid, Water

443.29°C (rough estimate)

348.863ºC

1.6500 (estimate)

0mmHg at 25°C

Xi

Maximum single oral doses of 5g/kg in mice and rats and 2 g/kg in dogs were not lethal.

In large registration trials of various forms of mesalamine, serum enzyme elevations were no more common with the products than with placebo therapy and were less common than with sulfasalazine. In these large studies, there were no reported instances of clinically apparent liver injury. Since approval and wide scale usage, however, there have been isolated reports of acute and chronic liver injury with jaundice attributed to mesalamine therapy. Clinically apparent liver injury is estimated to occur at an incidence of 3.2 cases per million prescriptions. Several patterns of injury have been reported, including asymptomatic and mild elevations in serum ALT levels, mild hepatitis accompanying a hypersensitivity reaction within a few days or weeks of starting (sometimes following a similar reaction to sulfasalazine), drug fever with accompanying serum enzyme elevations or mild hepatitis, and more typically, idiosyncratic cholestatic or hepatocellular liver injury (Cases 1 and 2), which typically arises after 1 to 6 months of treatment and is not accompanied by signs of hypersensitivity (rash, fever, eosinophilia). Most cases of liver injury with jaundice have been mild-to-moderate in severity and resolve rapidly upon stopping. In cases with hypersensitivity reactions, corticosteroid therapy is often used and appears to speed recovery. There have been no convincing reports of fatal acute liver injury, chronic hepatitis or vanishing bile duct syndrome attributable to mesalamine.

Olsalazine and olsalazine-S are more than 99% bound to plasma proteins. Mesalamine (5-ASA) is 74% bound to plasma proteins.

For the treatment of Inflammatory Bowel Disease and Ulcerative Colitis.

Mesalamine, also known as mesalazine and 5-aminosalicylate, is an orally available, antiinflammatory agent used for the treatment of ulcerative colitis to both induce and maintain remissions in disease. Mesalamine therapy has been associated with a low rate of serum enzyme elevations during therapy and with rare instances of clinically apparent acute liver injury.

Gastrointestinal Agents

Olsalazine is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease and Ulcerative Colitis. Olsalazine reduces the bowel inflammation, diarrhea (stool frequency), rectal bleeding, and abdominal pain. Olsalazine is thought to work like balsalazide, delivering mesalazine or 5-aminosalicylic acid past the small intestine to the large intestine to act on the site of disease.

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)|Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion. (See all compounds classified as Gastrointestinal Agents.)

After oral administration, olsalazine, has limited systemic bioavailability. 98-99% of the dose is converted to mesalamine (5-ASA) in the colon, which is absorbed slowly resulting in very high local concentrations in the colon.|Approximately 0.1% of an oral dose of olsalazine is metabolized in the liver to olsalazine-O-sulfate (olsalazine-S).The remaining 5-ASA is partially acetylated and is excreted in the feces.

Most (98 to 99%) of an oral dose is rapidly converted into two molecules of 5-aminosalicylic acid (5-ASA) by colonic bacteria and the low prevailing redox potential found in this environment. The conversion of olsalazine to mesalamine in the colon is similar to that of sulfasalazine, which is converted into sulfapyridine and mesalamine. Approximately 0.1% of an oral dose of olsalazine is metabolized in the liver to olsalazine-O-sulfate (olsalazine-S)

Olsalazine has an elimination half-life of 0.9 hours, however, olsalazine-S has a half-life of 7 days.

Orally administered olsalazine is converted to mesalamine which is thought to be the therapeutically active agent in the treatment of ulcerative colitis. The mechanism of action of mesalamine (and sulfasalazine) is unknown, but appears to be topical rather than systemic. Mucosal production of arachidonic acid (AA) metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes (LTs) and hydroxyelcosatetraenoic acids (HETEs) is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin (PG) production in the colon.

azodisal sodium

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