For the treatment of active ulcerative proctitis.
Although the mechanism of action of mesalazine is not fully understood, it appears to be topical rather than systemic. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalazine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon.
Oral, mouse: LD<sub>50</sub> = 3370 mg/kg; Oral, rat: LD<sub>50</sub> = 2800 mg/kg; Skin, rabbit: LD<sub>50</sub> = &gt;5 gm/kg. There have been no documented reports of serious toxicity in man resulting from massive overdosing with mesalamine. Under ordinary circumstances, mesalazine absorption from the colon is limited.
20 to 30% absorbed following oral administration. 10 to 35% absorbed from the colon (rectal suppository) - extent of absorption is determined by the length of time the drug is retained in the colon.
The mean elimination half-life was 5 hours for 5-ASA and six hours for N-acetyl-5-ASA following the initial dose. At steady state, the mean elimination half-life was seven hours for both 5-ASA and N-acetyl-5-ASA.
Approximately 28% of the mesalamine in Asacol tablets is absorbed after oral ingestion, leaving the remainder available for topical action and excretion in the feces. It is excreted mainly by the kidney as N-acetyl-5-aminosalicylic acid.