Mesalazine A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in Chronic Inflammatory Bowel Disease

Abstract

Mesalazine (5-aminosalicylic acid; mesalamine), the active moiety of sulphasalazine (salazosulfapyridine), is available in specially formulated oral and rectal forms for the treatment of active ulcerative colitis of mild to moderate severity and for maintenance therapy during disease remission. Tablets or capsules coated with acrylic-based resin and tablets containing microgranules coated with ethylcellulose deliver mesalazine to the distal small intestine and colon, thus avoiding the need for the carrier, sulphapyridine, which is responsible for many of the adverse effects associated with sulphasalazine. Since mesalazine is released in the small intestine from some coated preparations in contrast to sulphasalazine, these oral formulations have therapeutic potential in Crohn's disease. A limited number of therapeutic trials suggest that orally administered mesalazine 1.5 to 2.4g daily is of similar efficacy to sulphasalazine 2 to 3g daily in patients with mild to moderate ulcerative colitis. The efficacy of mesalazine enemas has been more widely investigated, a dose of 1 to 4g once daily being consistently more effective than placebo and apparently similar to enemas of prednisone 25mg or oral sulphasalazine 3g. Initial results suggest that mesalazine 4g enemas may be more effective than those containing hydrocortisone 100mg. Mesalazine and sulphasalazine in approximately equivalent oral dosages are similarly effective in maintaining remission in ulcerative colitis. Orally administered coated mesalazine is generally well tolerated by about 85% of patients allergic to or intolerant of sulphasalazine, the remainder experiencing similar reactions to both drugs. Adverse effects of mesalazine enemas are confined to local irritation and effects resulting from enema-tip insertion. Thus, orally administered coated mesalazine is a suitable alternative to sulphasalazine in the treatment of patients with mild to moderate active distal ulcerative colitis and for maintaining remission particularly in patients allergic to or intolerant of sulphasalazine. In patients who find enema therapy acceptable, mesalazine enemas are effective and well tolerated.

CD26 Expression Correlates with a Reduced Sensitivity to 2′-Deoxycoformycin-Induced Growth Inhibition and Apoptosis in T-Cell Leukemia/Lymphomas

“…Once we defined the constitutive expression of the complex CD26/ADA in T-cell lines, we investigated the effects of dCF on cell proliferation. In agreement with previous results (35), exposure of T-cell lines to increasing concentrations of dCF, if used alone, did not significantly impair the clonogenic growth of any of the cell lines tested, even at concentrations of dCF as high as 100 M (data not shown). Therefore, in vitro experiments were always carried out in the presence of the ADA substrate dAdo (35), used at a concentration of 10 M (clonogenic growth) or 25 M (liquid cultures), which did not directly impair cell survival in our cellular systems (data not shown).…”

“…As shown in the present and other studies, in vitro exposure to dCF alone is usually not sufficient to impair the growth or induce apoptosis of a given cell population (35). Therefore, experiments aimed to test the inhibitory effect of dCF usually require the presence of the ADA substrates dAdo and/or Ado (35) used in our as well as in other experiments (2,35), at fixed, nontoxic concentrations. This is in keeping with the main function of ADA to act as a detoxifying agent (4,5).…”

A Retrospective Case–Control Study Evaluating the Role of Mifepristone for Induction of Labor in Women with Previous Cesarean Section

“…Mifepristone stimulates labor as naturally as possible, which can be very beneficial especially in women with prior CS. Mifepristone leads to cervical ripening [21,22] (by stimulating the release of nitric oxide); promotes uterine contractions [23] (by increasing myometrial cell excitability, establishing gap junctions between cells and influx of calcium); and increases the release of prostaglandins by decidual cells [24,25], without acting as a direct uterotonic. As clearly shown in Fig.…”

Blockade of 5-HT2 Receptor Selectively Prevents MDMA-Induced Verbal Memory Impairment

“…The 75 mg dose of MDMA was selected because it falls within the normal range of and has been consistently shown to impair memory performance and produce robust subjective mood changes in a number of previous studies from our lab Ramaekers, 2005, 2007;Kuypers et al, 2006;Ramaekers et al, 2009). Doses of pindolol 20 mg and ketanserin 50 mg represent regular therapeutic doses that block B40% of 5HT 1A receptors and 91% of 5HT 2 receptors, respectively (Brogden and Sorkin, 1990;Rabiner et al, 2000;Sharpley et al, 1994).…”