5-ASA in ulcerative colitis: Improving treatment compliance (original) (raw)
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World Journal of Gastroenterology, 2013
AIM: To compare the mucosal concentrations of 5-aminosalicylic acid (5-ASA) resulting from different pharmaceutical formulations and analyse the influence of inflammation on the mucosal concentrations. METHODS: The study included 130 inflammatory bowel disease (IBD) patients receiving 5-ASA as pH-dependent-release formulations (73 patients), time-dependent-release formulations (11 patients), or pro-drugs (18 patients). In addition, 28 patients were receiving topical treatment (2-4 g/d) with pH-dependent-release formulations. Endoscopic biopsies were obtained from the sigmoid region during the colonoscopy. The 5-ASA concentrations (ng/mg) were measured in tissue homogenates using high-pressure liquid chromatography with electrochemical detection. The t test and Mann-Whitney test, when appropriate, were used for statistical analysis. RESULTS: Patients receiving pH-dependent-release formulations showed significantly higher mucosal concentrations of 5-ASA (51.75 ± 5.72 ng/mg) compared with patients receiving pro-drugs (33.35 ± 5.78 ng/mg, P = 0.01) or time-dependent-release formulations (38.24 ± 5.53 ng/mg, P = 0.04). Patients with endoscopic remission had significantly higher mucosal concentrations of 5-ASA than patients with active disease (60.14 ± 7.95 ng/mg vs 35.66 ± 5.68 ng/mg, P = 0.02). Similar results were obtained when we compared patients with the histological appearance of remission and patients with active histological inflammation (67.53 ± 9.22 ng/mg vs 35.53 ± 5.63 ng/mg, P < 0.001). Significantly higher mucosal concentrations of 5-ASA were detected in patients treated with both oral and topical treatments in combination compared with patients who received oral treatment with pH-dependent-release formulations alone (72.33 ± 11.23 ng/mg vs 51.75 ± 5.72 ng/mg, P = 0.03). CONCLUSION: IBD patients showed significant variability in mucosal 5-ASA concentrations depending on the type of formulation, and the highest mean concentration was achieved using pH-dependent-release formulations.
Aliment Pharmacol Therapeut, 2007
An oral multiparticulate coated formulation of 5-aminosalicylic acid (5-ASA ; mesalazine) has been developed to provide a controlled release of the drug, in a pH-dependent fashion, in the distal ileum and colon. The purpose of the present study was to assess the systemic availability of the drug and its metabolite, acetyl-5-ASA, following single (800 mg) and multiple (2400 mg for 56 days) oral dose administration. Methods : Three groups were investigated : six healthy volunteers, six patients with ulcerative colitis, and nine patients with Crohn's disease in remission. In the single oral dose study (800 mg) all three groups participated, whereas in the multiple oral dose study (2400 mg/day for 56 days) only the patients with inflammatory bowel disease took part. Plasma and urine 5-ASA and Ac-5-ASA were measured for 48 h. Resulls : In the single oral dose regimen, systemic absorption of 5-ASA and Ac-5-ASA were low and did not differ between the three groups. Only about 20% of the 5-ASA given was absorbed, with more than 80% of the drug being available in the terminal ileum and colon for therapeutic activity. The multiple oral dose regimen in patients with inflammatory bowel disease produced a significantly higher plasma concentration and urine excretion of both 5-ASA and Ac-5-ASA by the end of the treatment, in comparison to the first dose. There was a statistically higher systemic absorption of 5-ASA in patients with ulcerative colitis than in patients with Crohn's disease. After 56 days of dosing, no adverse event was reported and laboratory screening tests remained within normal ranges. Conclusions : The new oral 5-ASA formulation is gradually released throughout the small and large intestine, reflected by a low plasma concentration of the drug and its metabolite, with about SO% of the drug being available for ileum-colon therapeutic activity.
Alimentary Pharmacology & Therapeutics, 2009
Background 5-ASA-MMX® (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis.Aim To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol® (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study.Methods In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for ≥1 month prior to the trial, with ≥1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months’ treatment.Results In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated.Conclusions Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis.
A new 5-aminosalicylic acid multi-unit dosage form for the therapy of ulcerative colitis
European Journal of Pharmaceutics and Biopharmaceutics, 2001
The aim of the present study was to develop a multi-unit dosage form containing 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis (UC), optimised on the basis of recent studies indicating that UC patients have higher intestinal pH than was previously thought to be the case. Pellets with a drug content of 77.4% were prepared by a granulation and spheronization process and then coated with a new pH sensitive poly(meth)acrylate copolymer (Eudragit w FS 30D) to achieve site speci®c drug release close to the ileocecal valve. Dissolution tests were carried out in a paddle dissolution apparatus in media simulating pH conditions at various locations in the gastrointestinal tract. The pellets released rapidly at pH values above 7.5. Between 6.8 and 7.2 drug release was found to be zero order, while at pH 6.5 and below no release occurred. In a biorelevant medium which simulates the fasting proximal small intestine¯uid it was shown that neither surfactants (sodium taurocholate and lecithin) nor changes in ionic strength trigger drug release. Compared to 5-ASA pellets coated with the well established Eudragit w S, and to currently marketed products licensed for the treatment of UC, the multi-unit dosage form coated with the new polymer exhibited an in vitro dissolution pro®le more appropriate to the pH pro®le of the ileum and the colon observed in UC patients. q
INTERNATIONAL JOURNAL OF HEALTH SCIENCES (IJHS), 2019
Background and Aim: The development of new technologies for ulcerative colitis such as the matrix form of 5-aminosalicylic acid or mesalazine has already shown efficacy over placebo, but not over coated tablet form, which is usually used in clinical protocols for this disease management. Thus, this trial aimed at carrying out a systematic review to gather evidence that can reveal pre-eminence or equivalence in efficacy and safety of these two pharmaceutical forms in induction of remission in mild to moderate ulcerative colitis. Methods: Two independent researchers using Pubmed, Embase, Web of Science, Clinical Trials, Scopus and Science Direct databases and manual search selected eligible randomized clinical trials according to some preestablished inclusion criteria. This research was carried out from July 2016 to April 2019 without limitation of time interval or language, using clinical and endoscopic remission rates as primary endpoints of analysis. Results: Three studies met inclusion criteria and results have demonstrated that similar levels of endoscopic remission were achieved in both forms of the drug. However, clinical remission rates have suggested better results when mesalazine matrix was used. On the other hand, adverse effects were similar in both formulations, with headache and gastrointestinal disorders as the most representative ones. Conclusion: It was concluded that there are insufficient clinical studies to demonstrate the superiority of 5-ASA multi-matrix when compared with coated tablet during ulcerative colitis treatment. Consequently, it requires further clinical studies to add a deeper discussion on choosing a better therapy that can handle with this kind of disease.
Digestive Diseases and Sciences, 2011
Background Patients receiving 5-aminosalicylic acid (5-ASA) require long-term therapy to achieve good outcomes. Persistency (duration of time from initiation to discontinuation of therapy) is therefore an important consideration. Aim To evaluate persistency in patients receiving various oral 5-ASA formulations. Methods This retrospective, 12-month, cohort study examined new-starter patients (any age and diagnosis) from a large United States pharmacy database who filled a prescription for oral 5-ASA [Lialda Ò , Asacol Ò , Pentasa Ò 250 or 500 mg, balsalazide (generic and Colazal Ò ), and olsalazine (Dipentum Ò )] between March and September 2007. Persistency was evaluated monthly on the basis of prescription refill rates. Results Prescription and refill records were identified for 44,191 patients receiving oral 5-ASA. After 1 year, 20% of patients receiving Lialda were considered persistent and classified as continuing (refilling within a timeframe of up to twice the duration of the prescription), compared with 9% receiving Asacol, 7 (250 mg) and 10% (500 mg) receiving Pentasa, 10% receiving balsalazide, and 10% receiving Dipentum. Conclusions Overall persistency with oral 5-ASA therapy was low. However, patients receiving once-daily Lialda had significantly higher persistency after 1 year of treatment than patients receiving other oral 5-ASA therapies.
Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis
Gut, 1991
5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. Ali patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p<0-001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis.