Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009324 (ulcerative colitis)
 17,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty-four patients with active distal ulcerative colitis participated in a multicentre, randomized, investigator-blind trial to compare the effect of budesonide enema, 2 mg/100 ml, with prednisolone disodium phosphate enema, 31.25 mg/100 ml. Budesonide is a new potent corticosteroid with a rapid first-pass elimination. The patients were treated for 4 weeks, and the efficacy of the drugs were evaluated by sigmoidoscopy, histology, and subjective symptoms after 2 and 4 weeks. After 4 weeks of treatment 16 of 31 patients (52%) receiving budesonide enema had healed endoscopically, compared with 8 of 33 (24%) (p = 0.045) receiving prednisolone enema. Budesonide was superior to prednisolone in terms of both significantly improved sigmoidoscopic and histologic scores and subjective symptoms evaluated by visual analogue scales. The patients receiving prednisolone had a significant depression of endogenous cortisol levels during the treatment period, but not the patients receiving budesonide. Budesonide enema seems to be a promising therapy for active distal ulcerative colitis and causes no adverse reactions.
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PMID:A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis. 331 84

Budesonide-beta-D-glucuronide is a potentially useful orally administered prodrug for the treatment of colonic inflammatory bowel disease. Budesonide is a topically active glucocorticosteroid that exhibits low oral bioavailability (15%) in humans and laboratory animals. Oral delivery of budesonide to the inflamed tissues of the large intestine as its glucuronide prodrug should lead to locally high concentrations of active drug. Following liberation and absorption of the active drug, a large portion should be inactivated due to hepatic metabolism. Budesonide-beta-D-glucuronide was chemically stable in solutions at pHs of 1.5, 4.5, 6.5, and 7.4 at 37 degrees C. The enzymatic lability of the prodrug was assessed in luminal contents and mucosa obtained from conventional, germ-free, and colitic rats under in vitro conditions. There was a substantial change in glycosidase activity between the small intestine (proximal and distal portions) and the cecum in both conventional and colitic rat luminal contents. Luminal hydrolytic activity was low along the entire rat gastrointestinal tract of germ-free rats. Mucosal glycosidase activity was relatively low along the entire gastrointestinal tract of all three types of rats. The hydrolysis of prodrugs budesonide-beta-D-glucuronide and dexamethasone-beta-D-glucuronide in human fecal samples from patients with ulcerative colitis and normal volunteers was also measured. There were no statistically significant differences between the normal and colitic fecal samples for hydrolysis of the either prodrug or between the relative rates of hydrolysis of the two prodrugs. Hydrolysis rates of the prodrugs were about two orders of magnitude less in human fecal samples compared with those in cecal and colonic contents from the rat.
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PMID:Budesonide-beta-D-glucuronide: a potential prodrug for treatment of ulcerative colitis. 756 3

Budesonide is a glucocorticoid with high topical activity, but low systemic bio-availability which results in reduced systemic effects in comparison with other glucocorticoids. To date, it has been evaluated for use in patients with inflammatory bowel disease when administered either orally as a controlled ileal release formulation or rectally as an enema. In comparative trials, daily treatment with budesonide enema 2 mg/100ml for 4 weeks produced endoscopic remission or improvement in 46 to 84% of patients with active distal ulcerative colitis and/or proctitis and histological remission or improvement in 45 to 68%. In general, this regimen was effective as regimens of hydrocortisone, methylprednisolone, prednisolone or mesalazine (5-amino-salicylic acid, mesalamine) enemas, but caused less suppression of plasma cortisol levels than the other glucocorticoids. Oral treatment with controlled release budesonide 9 mg/day for 8 weeks produces clinical remission in 42 to 67% of patients with active Crohn's disease of the ileum, ileocaecal region and/or ascending colon and significantly reduces Crohn's disease activity index scores compared with baseline and placebo. Results of a quality-of-life questionnaire reflected these clinical improvements. Budesonide has similar efficacy to prednisolone. Response to budesonide is maintained after dosage tapering at 8 weeks. Compared with placebo, maintenance treatment with oral budesonide 3 or 6 mg/day increases the duration of remission in patients with Crohn's disease, but does not appear to affect the 1-year relapse rate. Thus, budesonide, administered rectally to patients with distal ulcerative colitis or proctitis or orally to patients with Crohn's disease of the ileum, ileocaecal region and/or ascending colon, is a favourable option for the treatment of acute exacerbations of inflammatory bowel disease. Because of the low incidence of adverse glucocorticoid-related effects associated with oral budesonide, it may also be a useful agent for longer term maintenance therapy if further clinical trials confirm its efficacy in this indication.
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PMID:Budesonide. A review of its pharmacological properties and therapeutic efficacy in inflammatory bowel disease. 858 30

This review focuses on current developments in the major categories of therapy used in the management of inflammatory bowel disease (IBD). Conventional corticosteroids, although a mainstay of the acute treatment of IBD for many years, have many drawbacks, including a variety of side effects--particularly with chronic use. Budesonide appears to be relatively safe and at least moderately effective in inducing remission in active distal ulcerative colitis (UC) and Crohn's disease. Aminosalicylates, both oral and topical, have proven useful in managing mild-to-moderate active UC and mild active Crohn's disease, as well as in maintaining remission. Data from recent trials suggest that higher doses of mesalamine are generally more efficacious than lower doses. In addition, a combination of oral and rectal formulations may succeed when one route, alone, is not successful. The immunomodulatory agents azathioprine, 6-mercaptopurine, and methotrexate have been shown to be effective in the treatment of IBD and are now widely accepted as valuable parts of the therapeutic armamentarium. Cyclosporine, although effective, is associated with many toxicities, and patients must be monitored closely in centers experienced with this agent. Clinical trials of IL-10, IL-11, and anti-TNFalpha have also shown promise. Antibiotics have been used empirically for many years in the treatment of IBD. Larger clinical trials are warranted to explore the potential efficacy of antibiotic therapy. This has been accomplished with metronidazole in Crohn's disease, and other antibiotic trials are underway at this time. The investigational agents acemannan, heparin, and transdermal nicotine have also shown variable degrees of promise as possible therapies for IBD. Despite the variety of agents available for the treatment of IBD, none is ideal or universally accepted. Ongoing research into the well-established therapeutic agents, as well as novel drugs with more precise targets, may contribute to the design of a more nearly optimal regimen for IBD in the not-too-distant future.
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PMID:Optimizing therapy for inflammatory bowel disease. 939 47

Inflammatory bowel disease therapy can be considered in several subcategories, and this review is designed to provide selective updates for some of the most important therapeutic entities currently marketed or soon to be available for the medical management of IBD. Although conventional corticosteroids have been a major component of acute inflammatory bowel disease management, steroids have many serious disadvantages; and toxicity is heightened with chronic steroid therapy. Newer corticosteroids, particularly budesonide, may be less toxic than older agents such as prednisone. Budesonide may be used as an enema in active distal ulcerative colitis (UC) or as delayed release tablets in Crohn's disease (CD). However, budesonide is not completely free from steroid side effects, and may share in some of the toxicity of older corticosteroids, particularly when high dose budesonide is administered. Topical and oral aminosalicylates are widely utilized for the treatment of mild to moderate active UC and mild active CD, and they also are efficacious for maintenance of IBD remission. Recent data continue to support the concept that higher doses and prolonged use of mesalamine-based drugs are therapeutically superior to lower doses and short term treatment. In addition, the combination of oral and rectal aminosalicylate formulations often succeeds in patients refractory to either used alone. The immunomodulatory drugs azathioprine and 6-mercaptopurine are particularly effective in treating both CD and UC, and methotrexate has also shown some promise in CD therapy. Immunosuppressive therapy for inflammatory bowel disease initially met with strong physician resistance. However, views have shifted in response to positive data on the utility of immunosuppressive agents in many cases of IBD. Although cyclosporine may be used as a 'rescue' medication in some severe IBD cases, it has been associated with severe toxic reactions. Possible candidates for cyclosporine treatment should be offered such therapy only in academic centers highly experienced with the nuances of this modality. Clinical trials of the newer entities IL-10, IL-11, tacrolimus, and anti-TNFalpha, have demonstrated variable efficacy in refractory IBD patients. Anti-TNFalpha has been very impressive, particularly in the presence of fistulizing Crohn's disease. Many physicians have utilized various antibiotics empirically as part of their 'general' management of IBD. Only metronidazole has been adequately studied in controlled CD trials, but other antibiotic studies are pending. Further exploration of antimicrobial treatment for IBD is clearly warranted. Many other investigational agents in disparate pharmaceutical categories have been employed in IBD therapy; and some of these also show varying degrees of promise, including the aloe vera derivative acemannan, several formulations of heparin, and both transdermal and intra-rectal nicotine. Despite the growing list of medications and formulations promoted for the treatment of IBD, no single drug or recognized combination has yet been confirmed as dependably clinically effective. Many additional investigations of IBD medical therapy are needed, including permutations of conventional medications, along with newer agents that may be more precisely targeted to specific aspects of IBD pathophysiology. All physicians who care for UC and CD patients enthusiastically await more optimal regimens for these challenging disorders.
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PMID:Medical therapy of inflammatory bowel disease for the 21st century. 1002 72

A groundswell of therapeutic modalities is presently sweeping through the field of inflammatory bowel disease (IBD), revolutionising the treatment and management of these disorders. At the forefront of newer agents are biological therapies, also referred to as 'biologics'. These include infliximab (cA2), CDP 571, rhIL-10, ICAM-1 antisense oligonucleotide (ISIS 2302) and opreleukin (rhIL-11). Among these, infliximab and CDP 571 are perhaps the most promising, particularly in Crohn's disease. Both are anti-TNF alpha monoclonal antibody formulations with proven efficacy at doses of 5 mg/kg for inducing remission in patients with moderate to severe refractory Crohn's disease. Infliximab is beneficial in the treatment of fistulous Crohn's disease as well. Anti-inflammatory cytokines such as rhIL-10 and opreleukin (rhIL-11) in early reports appear efficacious in Crohn's disease but not in ulcerative colitis. Budesonide, a second generation glucocorticoid, in an oral controlled ileal release capsule, is an attractive alternative to prednisone for treating active Crohn's disease of the distal ileum and proximal colon. Also available as an enema, budesonide's efficacy approximates that of prednisolone for inducing remission in active distal ulcerative colitis. Postoperative recurrences of Crohn's disease are a common clinical scenario. Recently, mesalazine, metronidazole and mercaptopurine have been re-evaluated in the postoperative setting. In the largest postoperative prophylaxis trial, mercaptopurine was superior to both placebo and mesalazine in preventing clinical, endoscopic and radiographic relapses. Finally, miscellaneous therapies such as transdermal nicotine, nicotine tartrate enemas and topical lidocaine used in pilot studies for ulcerative colitis have shown promise. Case reports of thalidomide and tacrolimus (FK 506) have reported beneficial effects in treating complicated, refractory Crohn's disease.
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PMID:Promising new agents for the treatment of inflammatory bowel disorders. 1056 35

Budesonide is a locally acting steroid with a high first-pass metabolism in the liver and low systemic effects. We performed the first pilot study comparing budesonide foam (1 mg/50 ml b.i.d.) with mesalazine enemas (4 g/60 ml o.d.). 33 patients from 3 centres were enrolled in this open randomized clinical trial. 16 patients got budesonide foam and 17 got mesalazine enemas. The drugs were administered for 4 weeks. Histological index (HI) and endoscopic index (EI) were assessed at day 1 and day 28, clinical activity index (CAI) at day 1, 14 and 28. For patients with left-sided colitis and proctosigmoiditis improvement was defined as decrease in CAI of > or = 2 points. For patients with proctitis improvement was defined as decrease in HI of > or = 1 point. The primary efficacy evaluation was performed with the intention to treat population (n = 32). Improvement was found in 67% of the patients in the budesonide group compared to 71% in the mesalazine group. There was no statistically significant difference between the groups. Adverse events were mild and rare in both groups. Both treatments had no significant influence on plasma cortisol. In this pilot study for distal ulcerative colitis budesonide foam is as safe and effective as mesalazine enema.
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PMID:[Budesonide foam as a new therapeutic principle in distal ulcerative colitis in comparison with mesalazine enema. An open, controlled, randomized and prospective multicenter pilot study]. 1082 Aug 60

Budesonide (BDS) is a potent corticosteroid that has important implications in the pharmacotherapy of inflammatory bowel disease, especially in the treatment of ulcerative colitis and Crohn's disease. BDS is available on the market in the form of enteric-coated preparations. However these products, similar to other available site-specific dosage forms, are not sufficiently selective to treat colonic inflammatory bowel disease. The objective of this study was to evaluate the efficacy of a new microparticulate system containing BDS, to treat experimentally induced colitis in rats. This microparticulate system consisted of BDS-containing hydrophobic cores, microencapsulated within an enteric polymer, which solubilizes at above pH 7, thus combining pH-sensitive and controlled-release properties. Colonic injury and inflammation were assessed by measuring colon/bodyweight ratio, myeloperoxidase (MPO) activity, and by scoring macroscopic and histological damage in colitic rats. Rats were treated orally with BDS, included in the developed system, once a day for 4 days after the induction of inflammation. A BDS suspension and BDS-containing enteric microparticles were included as control formulations in the experimental design. The administration of the new BDS delivery system significantly reduced the colon/bodyweight ratio compared with the administration of control formulations. Similarly, MPO activity and macroscopic and histological damage of the inflamed colonic segments decreased significantly when the BDS formulation was administered, compared with the results obtained after oral administration of the drug suspension. There were no significant differences, however, when the new treatment was compared with the control formulation consisting of simple enteric microparticles.
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PMID:Colon-specific delivery of budesonide from microencapsulated cellulosic cores: evaluation of the efficacy against colonic inflammation in rats. 1157 3

At this time, standard therapy for treatment of inflammatory bowel disease includes the use of glucocorticoids for moderate to severe Crohn's disease, severe ulcerative colitis, and moderate ulcerative colitis failing mesalamine. Although the majority of patients will have clinical improvement with glucocorticoids, a substantial minority of patients will later flare with attempts to withdraw therapy. Given the numerous potential side effects associated with glucocorticoids, every effort should be made to switch these patients to a less toxic medication. Historically, the most reliable agents have been azathioprine or 6-mercaptopurine. Infliximab is a relatively new medication but would be expected to be beneficial for weaning glucocorticoids for Crohn's disease patients. Methotrexate is another alternative for Crohn's disease. Budesonide and CDP571 are still in developmental phases but likely will be helpful in managing this patient population. Mesalamine, cyclosporine, mycofenalate mofetil, and thalidomide have less data available to support their use but may be helpful for some patients. 6-Thioguanine may be an alternative to patients who do not tolerate 6-mercaptopurine or azathioprine.
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PMID:Managing the glucocorticoid dependent inflammatory bowel disease patient. 1172 77

Budesonide, a topical corticosteroid, has proven useful for the management of Crohn's disease. Its efficacy is similar to prednisone but it has fewer side effects. A new pH-modified release capsule (Budenofalk) is probably efficacious in distal ulcerative colitis. The aim of the present study was to establish the pharmacokinetics, pharmacodynamics, and safety of two dosage regimens of budesonide capsules and to obtain efficacy information. Budenofalk 9 mg daily was administered as a single dose 9 mg in 8 patients and as three 3 mg doses in 7 patients with active distal ulcerative colitis for 8 weeks. Symptoms were assessed at three timepoints during the study: baseline, 4 and 8 weeks after start of treatment. Endoscopic evaluation and budesonide concentration in mucosal biopsy specimens was performed at 0 and 8 weeks. A pharmacokinetic profile and pharmacodynamic profile (cortisol, lymphocytes and neutrophils) was performed at day 5. In the 9 mg o.d. group, higher peak concentrations and systemic availability was found compared to the 3 mg t.i.d. group. Cortisol suppression was more pronounced after 9 mg o.d. than after 3 mg t.i.d. Lag-time, AUC and pharmacodynamic effects were comparable (14% mean decrease lymphocyte count and 26% mean increase neutrophil count). Mucosal biopsy specimens in the distal colon revealed significant budesonide levels with both regimens. After 8 weeks, 71% in the 9 mg o.d. group and 38% in the 3 t.i.d. group responded. The endoscopic index improved from 10 +/- 2 to 2 +/- 3 (p <0.001) with 9 mg o.d. and from 9 +/- 2 to 4 +/- 4.7 (p = 0.02) with 3 mg t.i.d. The pharmacokinetic and pharmacodynamic profiles found in this study indicate that Budenofalk reaches the distal part of colon and rectum, but further studies to validate the budesonide assay in the mucosa and comparison with a control group are necessary. This limited study suggests that Budenofalk is effective in distal colitis and side effects are rare. Based on these observations a large clinical trial using 9 mg o.d. is indicated to confirm efficacy and assess further possible side effects.
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PMID:Evaluation of oral budesonide in the treatment of active distal ulcerative colitis. 1551 Feb 33


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