Mecolzine Mechanism of Action

Pharmacotherapeutic group: Intestinal anti-inflammatory agents, Aminosalicylic acid and similar agents. ATC code: A07EC02.
PHARMACOLOGY: Pharmacodynamics: Mechanism of 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 also been demonstrated. Mesalazine (5-Aminosalicylic acid/5-ASA) may also function as a radical scavenger of reactive oxygen compounds.
Pharmacodynamic effects: Mesalazine, orally administered, acts predominantly locally at the gut mucosa and in the submucous tissue from the luminal side of the intestine. It is important, therefore, that mesalazine is available at the regions of inflammation. Systemic bioavailability/plasma concentrations of mesalazine therefore are of no relevance for therapeutic efficacy, but rather a factor for safety. In order to fulfil these criteria, Mecolzine 500 mg tablets are coated with Eudragit L and Eudragit S; they are thus gastro-resistant and release of mesalazine is pH-dependent.
Pharmacokinetics: General considerations of mesalazine: Absorption: Mesalazine absorption is highest in proximal gut regions and lowest in distal gut areas.
Biotransformation: Mesalazine is metabolised both pre-systemically by the intestinal mucosa and the liver to the pharmacologically inactive N-acetyl-5-aminosalicylic 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.
Toxicology: Preclinical safety data: Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity, carcinogenicity (rat) or toxicity to reproduction.
Kidney toxicity (renal papillary necrosis and epithelial damage in the proximal convoluted tubule or the whole nephron) has been seen in repeat-dose toxicity studies with high oral doses of mesalazine. The clinical relevance of this finding is unknown.