Safety and Effectiveness of Long-term Allopurinol–Thiopurine Maintenance Treatment in Inflammatory Bowel Disease

Gerven

et al. 2013

Aliment Pharmacol Ther

SUMMARY BackgroundTen percent of patients with autoimmune hepatitis (AIH) are nonresponsive or intolerant to thiopurine therapy. A skewed metabolism, leading to the preferential generation of (hepato)toxic thiopurine metabolites (6-MMPs) instead of the metabolic active 6-tioguanine (thioguanine) nucleotides (6-TGNs), may explain this unfavourable outcome. Co-administration of allopurinol to low-dose thiopurine therapy may effectively revert this deviant metabolism, as has been shown in inflammatory bowel disease.

Section: Resultsmentioning

confidence: 99%

Allopurinol safely and effectively optimises thiopurine metabolites in patients with autoimmune hepatitis

Gerven

et al. 2013

Aliment Pharmacol Ther

“…17 Moreover, long-term treatment with this combination is effective and well-tolerated in IBD patients. 16,18 The pharmacokinetic explanation of the substantial increase in 6-TGN and decrease in 6-MMPR concentrations upon combination therapy is not completely clarified, but may be explained by alterations in the activities of XO, TPMT and HGPRT. The aim of the present study was to observe possible effects of allopurinol and low-dose thiopurine combination therapy on XO, TPMT and HGPRT activities in IBD patients who previously failed thiopurine monotherapy, due to a skewed thiopurine metabolism.…”

Section: Introductionmentioning

confidence: 99%

The effect of allopurinol and low-dose thiopurine combination therapy on the activity of three pivotal thiopurine metabolizing enzymes: Results from a prospective pharmacological study

Seinen

Asseldonk

Journal of Crohn's and Colitis

et al. 2013

Introduction: Thiopurine therapy is often discontinued in inflammatory bowel disease (IBD) patients. The xanthine oxidase (XO) inhibitor allopurinol has previously shown to enhance thiopurine efficacy and to prevent adverse reactions, the mechanism of this beneficial interaction is not completely clarified. The aim of this study is to observe possible effects of allopurinol and low-dose thiopurine combination therapy on the activity of three pivotal thiopurine metabolizing enzymes. Methods: A prospective study of IBD patients failing thiopurine therapy due to a skewed thiopurine metabolism was performed. Patients were treated with allopurinol and azathioprine or mercaptopurine. Xanthine oxidase, hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and thiopurine S-methyl transferase (TPMT) activities, and thiopurine metabolites concentrations were measured during thiopurine monotherapy, and after 4 and 12 weeks of combination therapy. Conclusion: Allopurinol and thiopurine combination-therapy seems to increase HGPRT and decrease XO activity in IBD patients, which at least in part may explain the observed changes in thiopurine metabolite concentrations.

“…Allopurinol had been tested as a combined therapy with routinely used drugs such as sulfasalazines or steroids [44][45][46][47][48]85] . In 3 open studies on IBD, allopurinol combination therapy increased thioguanine nucleotide (6-TGN) levels to greater than with monotherapy levels Khan ( Table 1 ) [44][45][46] .…”

Section: Allopurinolmentioning

confidence: 99%

Antioxidant Supplements and Gastrointestinal Diseases: A Critical Appraisal

2017

The gastrointestinal tract digests and absorbs dietary nutrients, protects the body against physical and chemical damage from contents in its lumen, provides immunity against external antigens, and keeps an optimum environment for the gut microbiota. These functions cannot be performed normally in several diseases of which the following are discussed here: irritable bowel syndrome and inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Because these diseases are associated with oxidative stress, a host of antioxidant supplements are used for maintenance and recovery of the gut functions. However, the benefits of these supplements have not been established. The available 80 human trials were rated for levels of confidence and for benefits of the antioxidant supplements. For Crohn's disease, the supplements for which clear benefits occurred in at least 2 studies were allopurinol, Boswellia serrata (frankincense or shallaki), Artemesia species (wormwood), Tripterygium wilfordii (léi gōng téng), and omega-3 fatty acids. Similar beneficial supplements for ulcerative colitis were allopurinol, Matricaria chamomilla (chamomile), Curcuma longa (curcumin in turmeric), and omega-3 fatty acids. There was also a clear benefit for ulcerative colitis in 2 studies where a multiherbal Chinese medicine preparation and an Ayurvedic medicine preparation were used. For irritable bowel syndrome, there was only a marginal benefit of some of the antioxidant supplements. Thus, some antioxidant supplements may be beneficial at certain stages of specific diseases. This is consistent with the current concept that antioxidants act by inhibiting oxidative stress pathways in a tissue- and environment-specific manner and not by simply acting as scavengers.