Source: Web Search Revision Year: 2022 Publisher: FAES FARMA, S.A., Mรกximo Aguirre, 14, 48940 โ Leioa, Spain
Intestinal Antiinflammatory agents. Aminosalicylic acid and similar agents.
ATC code: A07EC02
Mecolzine 500 mg suppositories contains mesalazine, also known as 5-aminosalicylic acid, which has an anti-inflammatory effect through a mechanism that has not yet been fully established. Mesalazine has been shown to inhibit LTB4-stimulated migration of intestinal macrophages and thus may reduce intestinal inflammation by restricting migration of macrophages to inflamed areas. The production of pro-inflammatory leukotrienes (LTB4 and 5-HETE) in macrophages of the intestinal wall is inhibited. Mesalazine has been shown to activate PPAR-ฮณ receptors which neutralize nuclear activation of intestinal inflammatory responses.
Under trial conditions mesalazine inhibited the cyclooxygenase and thus, the release of thromboxane B2 and prostaglandin E2, but the clinical meaning of this effect is still unclear. Mesalazine inhibits the formation of platelet activating factor (PAF). Mesalazine is also an antioxidant; it has been shown to decrease formation of reactive oxygen products and to capture free radicals.
In clinical trials performed in patients with active distal ulcerative colitis (proctitis/proctosigmoiditis) treatment with mesalazine 500 mg and 1 g suppositories in different dosing regimens (o.d./b.i.d./t.i.d) was effective for inducing clinical, endoscopic and histologic remission of the disease. Long-term treatment with mesalazine suppositories was effective and safe for maintenance of remission in patients with distal ulcerative colitis.
In a clinical trial in 49 pediatric patients (5-17 years of age) with mild to moderate ulcerative proctitis treatment with mesalazine 500 mg suppositories o.d. achieved significant reduction in the disease activity index after 3 and 6 weeks.
The therapeutic activity of mesalazine depends on the local contact of the drug with the affected area of the intestinal mucosa.
Mecolzine 500 mg suppositories suppositories are designed to achieve high concentrations of mesalazine in the distal part of the intestinal tract with reduced systemic absorption. The action of suppositories covers the rectum.
Absorption after rectal administration is low, but depends on the dose, formulation and extent of the dispersion. Based on data quantities recovered in urine from healthy volunteers, in steady state, given a daily dose of 2 g (1 g x 2), it was found that approximately 10% of the dose is absorbed after suppository administration.
The plasma protein binding of mesalazine and acetyl-mesalazine is approximately 50% and 80%, respectively.
Mesalazine is metabolized pre-systemically by the intestinal mucosa and systemically in the liver in N-acetyl-mesalazine (acetyl-mesalazine). Colon bacteria are also responsible for some acetylation. Acetylation appears to be independent of the acetylator phenotype.
It is believed that acetyl-mesalazine is clinically inactive, but this still needs to be confirmed.
The plasma half-life of mesalazine is approximately 40 minutes and 70 minutes to acetyl-mesalazine.
Both substances are eliminated with urine and faeces. Urinary excretion is mainly comprised by acetyl-mesalazine.
In patients with hepatic and renal impairment, 5-ASA elimination rate (clearance) is decreased and this results in an increased concentration of mesalazine, that may increase the risk of adverse nephrotoxic effects.
Toxic renal effects have been demonstrated in all species tested. Rat and monkey dosages and plasma concentrations at the No Observed Adverse Effect Levels (NOAELs) exceed those used in humans by a factor of 2-7.2.
No significant toxicity associated with the gastrointestinal tract, liver or haematopoietic system in animals has been observed.
In vitro test systems and in-vivo studies showed no evidence of mutagenic effects. Studies on the tumourigenic potential carried out in rats showed no evidence of any substance-related increase in the incidence of tumours.
Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to fertility, pregnancy, embryo-foetal development, parturition or postnatal development.
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