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
| Autor: | D.P. van Asseldonk, G.J. Peters, Nienke Losekoot, A.A. van Bodegraven, Margien L. Seinen, N. K. H. de Boer, Gerd Bouma, Kees Smid, Cjj Mulder |
|---|---|
| Přispěvatelé: | Gastroenterology and hepatology, Medical oncology laboratory, CCA - Innovative therapy |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Hypoxanthine Phosphoribosyltransferase Xanthine Oxidase Combination therapy Allopurinol Metabolite Azathioprine Pharmacology Inflammatory bowel disease chemistry.chemical_compound Thioinosine Humans Medicine Prospective Studies Enzyme Inhibitors Xanthine oxidase Fatigue Thiopurine methyltransferase biology Mercaptopurine business.industry Gastroenterology Nausea Methyltransferases General Medicine Middle Aged Thionucleotides Inflammatory Bowel Diseases medicine.disease Guanine Nucleotides Enzyme Activation chemistry biology.protein Drug Therapy Combination Female business Immunosuppressive Agents medicine.drug |
| Zdroj: | Seinen, M L, van Asseldonk, D P, de Boer, K H N, Losekoot, N, Smid, K, Mulder, C J J, Bouma, G, Peters, G J & van Bodegraven, A A 2013, ' 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 ', Journal of Crohn's and Colitis, vol. 7, no. 10, pp. 812-819 . https://doi.org/10.1016/j.crohns.2012.12.006 Journal of Crohn's and Colitis, 7(10), 812-819. Elsevier |
| ISSN: | 1873-9946 |
| Popis: | 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. Results Of fifteen IBD patients, XO activity decreased from 0.18 (IQR 0.08–0.3) during thiopurine monotherapy to 0.14 (IQR 0.06–0.2) and 0.11 (IQR 0.06–0.2; p = 0.008) mU/hour/ml at 4 and 12 weeks, respectively. HGPRT activity increased from 150 (IQR 114–176) to 180 (IQR 135–213) and 204 nmol/(h × mg protein) (IQR 173–213; p = 0.013). TPMT activity seemed not to be affected. 6-Thioguanine nucleotide concentrations increased from 138 (IQR 119–188) to 235 (223–304) and to 265 pmol/8 × 10^8 (IQR 188–344), whereas 6-methyl mercaptopurine ribonucleotides concentrations decreased from 13230 (IQR 7130–17420) to 690 (IQR 378–1325) and 540 (IQR 240–790) pmol/8 × 10^8 at 4 and 12 weeks of combination therapy (both p 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|