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Pharmacotherapeutic group: Intestinal anti-inflammatory agents; aminosalicyclic aid and similar agents. ATC code: A07EC02.
Pharmacology: Pharmacodynamics: Mechanism action: The mechanism of the anti-inflammatory action is unknown. The results of in vitro studies indicate that inhibition of lipoxygenase may play a role.
Effects on prostaglandin concentrations in the intestinal mucosa have been demonstrated. Mesalazine (5-Aminosalicyclic acid/5-ASA) may also function as a radical scavenger of reactive oxygen compounds.
Pharmacodynamic effects: On reaching the intestinal lumen, rectally administered mesalazine has largely local effects on the intestinal mucosa and submucosal tissue.
Pharmacokinetics: General consideration of mesalazine: Absorption: Mesalazine absorption is highest in proximal gut regions and lowest in distal gut areas.
Biostransformation: Mesalazine is metabolized both pre-systematically by the intestinal mucosa and in the liver to the pharmacologically inactive N-acetyl-5-arninosalicylic acid (N-Ac-5-ASA). The acetylation seems to be independent of the acetylator phenotype of the patient. Some acetylation also occurs through the action of colonic bacteria. Protein binding of mesalazine and N-Ac-5-ASA is 43% and 78%, respectively.
Elimination: Mesalazine and its metabolite N-Ac-5-ASA are eliminated via the faeces (major part), renally (varies between 20 and 50%, dependent on kind of application, pharmaceutical preparation and route of mesalazine release, respectively) and biliary (minor part). Renal excretion predominantly occurs as N-Ac-5-ASA. About 1% of total orally administered mesalazine dose is excreted into the breast milk mainly as N-Ac-5-ASA.
Melanez Suppositories 500 mg specific: Distribution: Based on published data, technetium-labelled Melanez Suppositories 500 mg showed peak spread of the suppository that had melted due to body temperature after 2-3 hours. The spread was limited primarily to the rectum and rectosigmoid junction. Melanez Suppositories 500 mg are thus particularly suitable for treating proctitis (ulcerative colitis of the rectum).
Absorption: After both a single administration and after several weeks of long-term treatment with 500 mg mesalazine three times daily as Melanez Suppositories, peak plasma concentrations of 5-ASA were in the range of 0.1 to 1.0 ug/ml, those of the main metabolite N-Ac-5-ASA were in the range of 0.3 to 1.6 ug/ml. Peak plasma concentrations of 5-ASA are partially reached within the first hour of application.
Elimination: After a single rectal dose of 500 mg mesalazine, approximately 11% (within 72 hours) was recovered in the urine, and after several weeks of long-term treatment with 500 mg mesalazine three times daily as Melanez Suppositories, approximately 13% of the 5-ASA dose administered was recovered in the urine. Approximately 10% of a single administered dose was eliminated via the bile.
Melanez Suppositories 1 g specific: Distribution: Scintigraphic studies with a similar medicinal product, technetium-labelled Melanez Suppositories 500 mg showed peak spread of the suppository that had melted due to body temperature after 2-3 hours. The spread was limited primarily to the rectum and rectosigmoid junction. It is assumed that Melanez Suppositories l g act very similar and thus are particularly suitable for treating proctitis (ulcerative colitis of the rectum).
Absorption: Mean peak plasma concentration of 5-ASA after a single rectal dose of 1 g mesalazine (Melanez Suppositories 1 g) were 192±125 ng/ml (range 19-557 ng/ml), those of the main metabolite N-Ac-5-ASA were 402±211 ng/ml (range 57-1070 ng/ml). Time to reach the peak plasma concentration of 5-ASA was 7.1±4.9 h (range 0.3-24 h).
Elimination: After a single rectal dose of 1 g mesalazine (Melanez Suppositories 1 g) approx. 14% of the administered 5-ASA dose were recovered in the urine during 48 hours.
