Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new pentasa research articles will be listed here shortly after becoming available to us.
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Medical research on pentasa
Scand J Gastroenterol. 2008; 43(7): 842-8
Garcia Vilela E, De Lourdes De Abreu Ferrari M, Oswaldo Da Gama Torres H, Guerra Pinto A, Carolina Carneiro Aguirre A, Paiva Martins F, Marcos Andrade Goulart E, Sales Da Cunha A
OBJECTIVE: Crohn's disease (CD) is characterized by a reduction in mucosal integrity that permits antigen penetration into the intestinal tissue. The administration of probiotics has been suggested to improve the barrier function of the mucosa. The objective of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability in CD. MATERIAL AND METHODS: Thirty-four patients were randomized according to the Vienna classification for treatment with either placebo or Saccharomyces boulardii. Baseline medications (mesalamine, azathioprine, prednisone, metronidazole and/or thalidomide) were maintained. Intestinal permeability (lactulose/mannitol ratio) was evaluated immediately before the beginning of treatment and at the end of the first and third treatment month. Fifteen healthy volunteers were also submitted for the intestinal permeability test. RESULTS: In volunteers, the lactulose/mannitol ratio was 0.005+/-0.0037, whereas this value was 0.021+/-0.01 in patients with CD (p=0.001). In the placebo group, there was an increase in lactulose/mannitol ratio by 0.004+/-0.010 (p=0.12) at the end of the third month. In the S. boulardii group, there was an improvement in intestinal permeability, with a decrease in the lactulose/mannitol ratio by 0.008+/-0.006 (p=0.0005) in the same period. CONCLUSIONS: Patients with CD in remission present alterations in the integrity of the intestinal mucosal barrier according to lactulose/mannitol ratio. S. boulardii added to baseline therapy improved intestinal permeability in these patients, even though complete normalization was not achieved.
Int J Pharm. 2008 Apr 30;
Fadda HM, Mohamed MA, Basit AW
Recently, there has been concern by regulatory authorities of the risk of alcohol-induced dose dumping of oral modified release (MR) formulations. The aim of this work was to use in vitro dissolution methodology to investigate the vulnerability of MR products to alcohol under different physiological conditions of the upper gastrointestinal tract. A variety of dissolution scenarios with ethanol concentrations in the range of 5-40% v/v were explored. Mesalazine (5-aminosalicylic acid) was selected as the model drug and the release behaviour of three commercially available MR, monolithic and multi-particulate preparations with pH-dependent or independent release mechanisms was evaluated (Salofalk((R)), Asacol((R)) and Pentasa((R))). Each product was found to have a distinctive release profile and behaved differently in the scenarios screened. In the case of Pentasa, complete dose dumping occurred on exposure to 40% ethanol in acid for 2h. Asacol, however, displayed a contrarian trend with drug release being substantially delayed in small intestinal media after pre-exposure to acid/ethanol for the same duration. Salofalk underwent accelerated drug release in the presence of ethanol in the dissolution media, with unexpected trends observed between the different scenarios. For the three preparations explored, there appears to be a complex interplay between the various formulation variables and ethanol in the dissolution media. The unpredictable release profiles under the different conditions makes it necessary to screen several in vitro scenarios of ethanol exposure for each preparation before a decision is reached on its susceptibility to drug release impairment on consumption with ethanol.
Rev Gastroenterol Disord. 2008; 8(1): 21-30; quiz 31-2
Lichtenstein GR, Rubin DT, Sabesin SM, Velayos FS, Vitat P
Recent evidence suggests that there is a link between increased colonic inflammation and risk of colorectal cancer, stressing the importance of preventing relapse. The risk of relapse is associated with several factors, of which the foremost is patient nonadherence to prescribed medical therapy. Nonadherence may be affected by such factors as complicated dosing regimens, forgetfulness, male sex, and treatment delivery methods. Mesalamine is the standard, first-line therapy and the treatment of choice for inducing and maintaining clinical and endoscopic remission of inflammation in patients with mild-to-moderate ulcerative colitis. Novel formulations of mesalamine and newly devised, high-dose regimens offer additional therapeutic options and may lead to improved treatment adherence, longer-lasting periods of remission, and enhanced patient well-being.
Mesalamine for inflammatory bowel disease: recent reappraisals.
Inflamm Allergy Drug Targets. 2008 Mar; 7(1): 1-5
Actis GC, Pazienza P, Rosina F
Derived from the historical molecule sulfasalazine, mesalamine has remained one of the mainstays for treatment of inflammatory bowel disease in the last 50 years. Recent advancement in both clinical and basic research has led to reappraise the drug under two crucial aspects. Firstly, there has been a re-evaluation of the chemo-protective effect of mesalamine against sporadic colorectal cancer. Evidence that inflammation plays a strong role in tumor induction from one side, and demonstration that mesalamine can touch on specific molecular steps enhancing apoptosis on the other side have re-shaped the indications of mesalamine for ulcerative colitis. Secondly, the role of thiopurines (azathioprine and 6-MP) in the maintenance of remission of ulcerative colitis has been reiterated by the results of several clinical trials. During attempts at clarifying the reasons why certain patients appear to be resistant to thiopurines, it was interestingly found that mesalamine can interfere thiopurine metabolism, causing an increased blood concentration of the specific immunosuppressive metabolites and a sequential enhancement of drug effectiveness. Mesalamine is therefore being studied as a means to overcome the genetically determined resistance to thiopurines. Such sharpened indications have reiterated attention to correct dosing: the results of controlled trials have shown mesalamine to be fully effective at twice the traditional daily dosage (4.8 grams instead of 2.4). The attendant problems of compliance seem to find solution in the availability of multi-matrix system formulations. This mesalamine story reminds us that in the absence of an etiological target capable to guide research to trace one abrogating molecule, (as it has happened for viral hepatitides for example), treatment of inflammatory bowel disease remains anti-inflammatory in nature and thus multifaceted. Besides justified use of cutting-edge technology to find novel molecules, smart re-evaluation of what is already in our hands can sometimes bring about unexpected breakthroughs.
World J Gastroenterol. 2008 May 14; 14(18): 2851-7
Guijarro LG, Mate J, Gisbert JP, Perez-Calle JL, Marin-Jimenez I, Arriaza E, Olleros T, Delgado M, Castillejo MS, Prieto-Merino D, Gonzalez Lara V, Pena AS
AIM: To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients. METHODS: Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo (group B). Patients were monitored using the Modified Truelove-Witts Severity Index (MTWSI). The primary endpoint was clinical remission (MTWSI = 2 points) and drug safety. The serum TNF-alpha, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS: Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine (group A) and mesalamine plus placebo (group B) respectively (OR = 1.71; 95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MTWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) after 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5). Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups. CONCLUSION: In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone), the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.
Once-daily MMX mesalamine for the treatment of mild-to-moderate ulcerative colitis.
Ther Clin Risk Manag. 2007 Oct; 3(5): 919-27
Kedia P, Cohen RD
First-line therapies in the treatment of patients with mild-to-moderate ulcerative colitis are sulfasalazine or one of the mesalamine derivatives. Mesalamine is popular given its safety profile and reasonable efficacy in many patients. However, compliance is poor with regimens demanding large number of pills dosed multiple times a day and non-compliance has been correlated with disease relapse. Mesalamine requires direct contact with the inflamed colonic mucosa. To avoid proximal absorption, a variety of delivery systems has been utilized to time the release of active mesalamine to the areas affected by colitis. The most common mesalamine release mechanisms include azo-bond prodrug carriers, pH-dependent dissolution, and moisture-sensitive product dispersion. Novel technology has resulted in the development and FDA-approval of a multi-matrix release (MMX) mesalamine. Pharmacodynamic studies suggest a reliable drug delivery system with homogenous release throughout the entire colon. By incorporating the largest amount of mesalamine (1.2 g) per pill, this new product dramatically decreases the number of pills needed to attain a therapeutic daily dosage, and is the first agent approved at once-daily dosing. These factors are expected to increase patient compliance with prescribed mesalamine dosing, and in turn decrease relapse rates of active ulcerative colitis.
The role of mesalamine in the treatment of ulcerative colitis.
Ther Clin Risk Manag. 2007 Oct; 3(5): 893-903
Karagozian R, Burakoff R
Ulcerative colitis (UC) is a chronic inflammatory condition of unclear etiology affecting the large bowel, most commonly the rectum and extending proximally in a continuous fashion. The overall principle in the pathophysiolgy of ulcerative colitis is the dysregulation of the normal immune system against an antigenic trigger leading to a prolonged mucosal inflammatory response. The diagnosing of UC is made by combining the clinical picture, tissue biopsy with the endoscopic appearance of mucosal ulceration, friable, edematous, erythematous granular appearing mucus. The approach to therapy of UC has been dependent on severity of symptoms with frontline therapy being salicylate based sulfasalazine. Newer formulations of salicylates based drugs with fewer side-effects have been developed. These are free of the sulphur component and are composed of 5-ASA, without the sulfapyridine carrier molecule. Mesalamine is one of these 5-ASA based agents that are currently available and indicated for treatment of UC. In mild/moderate active disease mesalamine has response rates between 40%-70% and remission rates of 15%-20%. Considering that the efficacy of 5-ASA is dose dependent, 4.8 g/day and 2.4 g/day have been shown to be the optimal dosages for mild-moderate distal active disease and for maintenance therapy, respectively. Patients with moderately active ulcerative colitis treated with 4.8 g/d of mesalamine are significantly more likely to achieve overall improvement at week 6 compared to patients treated with 2.4 g/d. In the setting of left-sided distal colitis (proctitis), topical (rectal) formulations have been found to be superior to oral aminosalicylates at inducing remission. Mesalamine has been shown to be safe in short term use with a dose-response efficacy without dose-related toxicity.
Dig Dis Sci. 2008 May 10;
Stocco G, Martelossi S, Malusa' N, Marino S, Decorti G, Bartoli F, Ventura A
Inflamm Bowel Dis. 2008 May 1;
Domènech E, Vega R, Ojanguren I, Hernández A, Garcia-Planella E, Bernal I, Rosinach M, Boix J, Cabré E, Gassull MA
Background: Cytomegalovirus (CMV) infection has been reported in ulcerative colitis (UC), especially in severe, steroid-refractory disease. However, its role in steroid-refractoriness remains unknown. Our goals were to evaluate the prevalence of CMV disease in UC, the best diagnostic strategy, and the influence of disease activity and/or treatment in its development.Methods: Prospective, observational study including 114 subjects with active UC requiring intravenous steroids, steroid-refractory UC, inactive UC on mesalamine, inactive UC on azathioprine, and healthy controls. CMV antibodies, pp65-antigenemia, and rectal biopsies for hematoxylin and eosin staining, immunohistochemistry, and CMV-pp67 mRNA were performed. These procedures were repeated after medical treatment only in patients with active UC. CMV disease was defined by the presence of inclusion bodies and/or positive immunohistochemistry in colonic biopsies.Results: CMV disease was found in 6 steroid-refractory, CMV-IgG-positive UC patients but not among controls, inactive UC, or steroid-responding UC patients. In 5 out of the 6 patients, CMV disease was diagnosed after 7-10 days on cyclosporine.Conclusions: CMV disease in UC only affects seropositive, steroid-refractory UC patients. Steroid/cyclosporine treatment together with disease activity may predispose to latent colonic CMV reactivation. The impact of antiviral therapy on the clinical outcome of these patients remains to be elucidated.(Inflamm Bowel Dis 2008).
MMW Fortschr Med. 2008 Mar 13; 150(11): 44-5