Trial reportEuropean journal of clinical pharmacology2013
Low allopurinol doses are sufficient to optimize azathioprine therapy in inflammatory bowel disease patients with inadequate thiopurine metabolite concentrations.
Trial report in European journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Effects of allopurinol on 6-mercaptopurine metabolism in unselected patients with pediatric acute lymphoblastic leukemia: a prospective phase II study.Haematologica · 2024Trial
- Low-Dose Azathioprine in Combination with Allopurinol: The Past, Present and Future of This Useful Duo.Digestive diseases and sciences · 2022Review
- Review
- Real-World Use of Azathioprine Metabolites Changes Clinical Management of Inflammatory Bowel Disease.Journal of the Canadian Association of Gastroenterology · 2021Article
- Optimizing Thiopurine Therapy with a Xanthine Oxidase Inhibitor in Patients with Systemic Autoimmune Diseases: A Single-Centre Experience.The Canadian journal of hospital pharmacy · 2021Article
- Thiopurines with low-dose allopurinol (ThiLDA)-a prospective clinical one-way crossover trial.European journal of clinical pharmacology · 2019Article
- Revisiting the Role of Thiopurines in Inflammatory Bowel Disease Through Pharmacogenomics and Use of Novel Methods for Therapeutic Drug Monitoring.Frontiers in pharmacology · 2018Review
- Azathioprine with Allopurinol: Lower Deoxythioguanosine in DNA and Transcriptome Changes Indicate Mechanistic Differences to Azathioprine Alone.Inflammatory bowel diseases · 2017Article
- Antioxidant Supplements and Gastrointestinal Diseases: A Critical Appraisal.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2017Article
- Monitoring thiopurine metabolites in inflammatory bowel disease.Frontline gastroenterology · 2016Review
- Pharmacology and Optimization of Thiopurines and Methotrexate in Inflammatory Bowel Disease.Clinical pharmacokinetics · 2016Review
- Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease.World journal of gastroenterology · 2014Review
- Pediatric ulcerative colitis: a practical guide to management.Paediatric drugs · 2014Review
- Concomitant 5-aminosalicylic acid treatment does not affect 6-thioguanine nucleotide levels in patients with inflammatory bowel disease on thiopurines.Annals of gastroenterologyArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeRecent studies in patients with inflammatory bowel diseases (IBD) on thiopurine therapy suggest that too low 6-thioguanine nucleotide concentrations (6-TGN) and too high methylmercaptopurine nucleotide concentrations (MMPN) can be reversed by a combination therapy of allopurinol and low-dose thiopurines. To date, however, optimal dosing has not been established. The aim of this study was to evaluate the minimal allopurinol doses necessary to achieve adequate 6-TGN concentrations in combination with low-dose azathioprine.
methodsA stepwise dose-escalation of allopurinol was performed in 11 azathioprine-pretreated IBD patients with inadequately low 6-TGN concentrations (<235 pmol/8 × 10(8) erythrocytes) and/or elevated MMPN concentrations (>5,000 pmol/8 × 10(8) erythrocytes) and/or elevated liver enzymes (alanine aminotransferase and/or aspartate aminotransferase levels one- to threefold the upper limit of normal). Six patients were recruited into an open study, and five were treated in the context of an individualized therapeutic approach. Adverse effects, azathioprine metabolites, liver enzymes and whole blood counts were monitored two to three times per month.
resultsAdequate 6-TGN concentrations were achieved with a combination of 25 mg allopurinol and 50 mg azathioprine in one patient and with 50 mg allopurinol and 50 mg azathioprine in nine patients. Median 6-TGN concentrations (range) were 336 (290-488) pmol/8 × 10(8) erythrocytes after an 8-week-long intake of the final dose combination. One patient dropped out due to nausea after the first intake. MMPN concentrations and liver enzymes normalized immediately in all affected patients. All patients finishing the dose-escalation regimen tolerated the treatment without toxicity.
conclusionsCombination therapy with only 50 mg allopurinol and 50 mg azathioprine daily is sufficient, efficacious and safe in most IBD patients with inadequate thiopurine metabolite concentrations to optimize azathioprine-based IBD therapy.
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