Source: Web Search Publisher: FAES FARMA, S.A., C/Máximo Aguirre, 14, 48940 Leioa (Bizkaia), Spain
Pharmacotherapeutic group: Aminosalicylic acid and similar
Code ATC: A07EC02
Mesalazine is one of the two components of sulfasalazine, the other being sulfapyridine. While mesalazine is the active fraction, sulfapyridine is responsible for most adverse events associated with therapy with sulfasalazine.
Although the anti-inflammatory mechanism of action of 5-ASA is unknown, several possibilities are considered:
The most recent data suggest that 5-ASA is a biological antioxidant and its activity is based on the uptake of oxygen free radicals. In this activity, 5-ASA differs from sulfasalazine, sulfapyridine, Nacetyl-5-ASA (Ac-5-ASA) and other salicylates.
After the administration of oral doses of 500 mg of mesalazine t.i.d. to patients with ulcerative colitis, the steady-state mean plasma concentrations of 5-ASA and Ac-5-ASA (major metabolite) are 0.7 µg/ml and 1.2 µg/ml, respectively. The peak plasma levels with the retard release forms are obtained at 5 h post-administration. Recovery (at the highest dose) in urine (44%) and faeces (35%) shows that 5-ASA is available for its local and systemic action. In fasting healthy subjects, the peak plasma concentration of 1.3 µg/ml and 2.3 µg/ml of 5-ASA and Ac-5-ASA respectively was obtained at 6 h post-administration.
Acetylation of 5-ASA occurs in the liver and the colon wall, regardless of the acetylator status. It appears that the acetylation process is saturable; however, at therapeutic doses (250-500 mg) neither the peak plasma concentration nor the area under the curve of plasma concentration vs. time for 5-ASA evidenced any deviation from linearity of the dose in the steady state.
After oral administration, 5-ASA is cleared at a high percentage as Ac-5-ASA both in urine and in faeces. In fact, over 90% of the drug identified in urine is in metabolite form.
Non clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity, carcinogenic and toxicity to reproduction and development.
Kidney toxicity (renal papillary necrosis and ephithelial damage in the proximal tubule (pars convoluta) or the whole neprhon) has been seen in repeated-dose toxicity studies with high oral doses of mesalazine.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
