mercaptopurine and Colonic-Diseases

Fistulas are common in patients with Crohn's disease and, when associated with inflammatory disease and established for several weeks, tend to be chronic. Perianal fistulas are the most frequent complication of, and are most often associated with, colonic disease. Perianal fistulas commonly require surgical resection and permanent ileostomy. Antibiotics, cyclosporine, methotrexate and thalidomide have been used in uncontrolled trials; only azathioprine, 6-mercaptopurine and infliximab have been assessed in double-blind, placebo controlled studies. Relapse of the fistula occurs with all drugs, unless treatment is continued long term. Each drug differs in its onset of action and long term tolerability. An approach to fistulizing disease in Crohn's disease is suggested.

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Azathioprine; Colonic Diseases; Crohn Disease; Cyclosporine; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Infliximab; Intestinal Fistula; Mercaptopurine; Methotrexate; Rectal Fistula; Thalidomide

6-MP has short elimination time (<2 h) and low bioavailability (~ 50%). Present study was aimed to develop time controlled and site targeted delivery of 6-Mercaptopurine (6-MP) for treatment of colon diseases.. Compression coating technique was used. 32 full factorial design was designed for optimization of the outer coat for the core tablet. For outer coat amount of Eudragit RS 100 and hydroxypropyl methylcellulose (HPMC K100) were employed as independent variables each at three levels while responses evaluated were swelling index and bursting time. Direct compression method was used for tablets formulation.. 80% w/w of microcrystalline cellulose and 20% w/w of croscarmellose sodium were found to be optimum concentration for the core tablet. The outer coat of optimized batch (ED) contains 21.05% w/w Eudragit RS 100 and 78.95% w/w HPMC K100 of total polymer weight. In-vitro dissolution study indicated that combination of polymer retards the drug release in gastric region and releases ≥95% of drug in colonic region after ≥7 h. Whereas in case of in-vivo placebo x-ray imaging study had shown that the tablet reaches colonic part after 5±0.5 h providing the proof of arrival in the colon. Stability study indicated that the optimized formulation were physically and chemically stable.. Present research work concluded that compression coating by Eudragit RS 100 and HPMC K100 to 6-MP core provides potential colon targeted system with advantages of reduced gastric exposure and enhanced bioavailability. Formulation can be considered as potential and promising candidate for the treatment of colon diseases.

Topics: Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Colonic Diseases; Humans; Mercaptopurine; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Tablets; Time and Motion Studies

Topics: Adult; Biomarkers; Biopsy; Colon; Colonic Diseases; Colonoscopy; Drug Therapy, Combination; Female; Gastrointestinal Agents; Histiocytosis, Langerhans-Cell; Humans; Immunohistochemistry; Mercaptopurine; Predictive Value of Tests; Prednisolone; Time Factors; Treatment Outcome; Vinblastine

Acute severe lower gastrointestinal bleeding in Crohn's disease is uncommon, but is a diagnostic and therapeutic challenge. We aimed to identify risk factors for acute lower gastrointestinal bleeding in patients with Crohn's disease and assess the cumulative probability of rebleeding in relation to therapeutic modality.. We retrospectively reviewed the medical records of 70 Crohn's patients (4.0%) with acute severe lower gastrointestinal bleeding and compared these with matched 140 Crohn's patients without bleeding.. The cumulative probability of bleeding after diagnosis of Crohn's disease was 1.7%, 3.6%, 6.5%, and 10.3% after 1, 5, 10, and 20 years respectively. At presentation, the median haemoglobin concentration was 8.4g/dL (range, 4.7-11.6g/dL). Use of azathioprine/6-mercaptopurine decreased the risk of lower gastrointestinal bleeding (OR: 0.525, 95% CI: 0.304-0.906, p=0.021). Bleeding recurred in 29 patients (41.4%) after a median time of 3.2 months (range, 15 days-94.7 months). One out of eleven patients treated with infliximab rebled. The cumulative probability of rebleeding tended to be lower in patients treated with infliximab than in those receiving other treatments (p=0.076).. Azathioprine/6-mercaptopurine may reduce the risk of acute severe lower gastrointestinal bleeding. The rebleeding is common, but infliximab may decrease rebleeding.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Asian People; Azathioprine; Blood Transfusion; Case-Control Studies; Colonic Diseases; Crohn Disease; Embolization, Therapeutic; Female; Gastrointestinal Hemorrhage; Hemoglobins; Hemostasis, Endoscopic; Humans; Ileal Diseases; Immunosuppressive Agents; Infliximab; Kaplan-Meier Estimate; Male; Mercaptopurine; Middle Aged; Recurrence; Republic of Korea; Retrospective Studies; Risk Factors; Young Adult

Topics: Azathioprine; Colonic Diseases; Crohn Disease; Gastrointestinal Agents; Hemangioendothelioma; Hemangioma; Humans; Ileal Diseases; Immunocompromised Host; Immunologic Factors; Immunosuppressive Agents; Male; Mercaptopurine; Middle Aged; Splenic Neoplasms; Tumor Necrosis Factor-alpha

Nineteen patients (12 children and 7 adults) with severe Crohn's disease, all of whom were dependent on corticosteroids, were treated with 6-mercaptopurine. All patients received a daily dose of 6-mercaptopurine of 50 mg; in two pediatric patients with a poor response after 2 months, the dosage was increased to 75 mg/day. A complete or partial response to 6-mercaptopurine therapy was noted in 47% of patients, and therapy failed in 53%. The age of the patients, prior resection, or initial symptoms did not influence the response. The clinical response was better in male than in female patients and in patients with involvement of both the small intestine and the colon than in those with only enteritis. 6-Mercaptopurine is a possible alternative to long-term corticosteroid therapy or surgical treatment in selected patients with severe Crohn's disease.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Child; Colonic Diseases; Crohn Disease; Female; Follow-Up Studies; Humans; Intestine, Small; Male; Mercaptopurine; Metronidazole; Middle Aged; Remission Induction; Retrospective Studies; Sulfasalazine; Time Factors

The radiographic and endoscopic features of the colonic ulcers during the course of a case of systemic lupus erythematosus are illustrated. Barium enema revealed the "collar button" type of penetrating ulcers in the left half of the colon and endoscopy demonstrated multiple round- or oval-shaped discrete ulcers, so-called "punched-out" ulcers with pale mucosa. These findings are compared with those of the reported cases of systemic lupus erythematosus and ulcerative colitis. Steroid and 6-mercaptopurine therapy was effective in this case.

Topics: Adult; Colitis, Ulcerative; Colonic Diseases; Diagnosis, Differential; Endoscopy; Female; Humans; Lupus Erythematosus, Systemic; Mercaptopurine; Prednisolone; Radiography; Ulcer