ArticleBritish journal of clinical pharmacology2008
IMPDH activity in thiopurine-treated patients with inflammatory bowel disease - relation to TPMT activity and metabolite concentrations.
Article in British journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Impact of NUDT15 polymorphisms on thiopurines-induced myelotoxicity and thiopurines tolerance dose.Oncotarget · 2017Pooled it
- Azathioprine Inhibits Hepatitis A Virus Replication In Vitro.Pathogens (Basel, Switzerland) · 2026Article
- Antiviral Potential of Azathioprine and Its Derivative 6- Mercaptopurine: A Narrative Literature Review.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Pharmacogenetics of Drug Therapies in Rheumatoid Arthritis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Precision therapy of 6-mercaptopurine in Chinese children with acute lymphoblastic leukaemia.British journal of clinical pharmacology · 2020Article
- Tests that now deserve to be more widely adopted in IBD clinical practice.Therapeutic advances in gastroenterology · 2020Review
- New methods to assess 6-thiopurine toxicity and expanding its therapeutic application to pancreatic cancerMedChemComm · 2019Article
- Efforts in redesigning the antileukemic drug 6-thiopurine: decreasing toxic side effects while maintaining efficacy.MedChemComm · 2019Article
- Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping.Journal of gastroenterology · 2018Review
- Revisiting the Role of Thiopurines in Inflammatory Bowel Disease Through Pharmacogenomics and Use of Novel Methods for Therapeutic Drug Monitoring.Frontiers in pharmacology · 2018Review
- Article
- NUDT15 R139C-related thiopurine leukocytopenia is mediated by 6-thioguanine nucleotide-independent mechanism in Japanese patients with inflammatory bowel disease.Journal of gastroenterology · 2016Article
- Monitoring thiopurine metabolites in korean pediatric patients with inflammatory bowel disease.Yonsei medical journal · 2014Article
- New genetic biomarkers predicting azathioprine blood concentrations in combination therapy with 5-aminosalicylic acid.PloS one · 2014Article
- Monitoring and safety of azathioprine therapy in inflammatory bowel disease.Pediatric gastroenterology, hepatology & nutrition · 2013Review
- Gene expression and thiopurine metabolite profiling in inflammatory bowel disease - novel clues to drug targets and disease mechanisms?PloS one · 2013Article
- Pharmacogenetic determinants of mercaptopurine disposition in children with acute lymphoblastic leukemia.European journal of clinical pharmacology · 2012Review
- Accuracy of genotyping using the TaqMan PCR assay for single nucleotide polymorphisms responsible for thiopurine sensitivity in Japanese patients with inflammatory bowel disease.Experimental and therapeutic medicine · 2011Article
- The multidrug-resistance protein 4 polymorphism is a new factor accounting for thiopurine sensitivity in Japanese patients with inflammatory bowel disease.Journal of gastroenterology · 2010Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAzathioprine and 6-mercaptopurine are steroid-sparing drugs used in inflammatory bowel disease (IBD). The polymorphic enzyme thiopurine S-methyltransferase (TPMT) is of importance for thiopurine metabolism and occurrence of adverse events. The role of other thiopurine-metabolizing enzymes is less well known. This study investigated the role of inosine-5'-monophosphate dehydrogenase (IMPDH), which is a key enzyme in the de novo synthesis of guanine nucleotides and also strategically positioned in the metabolic pathway of thiopurines.
methodsIMPDH was measured in 100 healthy blood donors. IMPDH, TPMT and metabolite concentrations were studied in 50 patients with IBD on stable thiopurine therapy. IMPDH activity was measured in peripheral blood mononuclear cells. TPMT activity, 6-methylthioinosine 5'-monophosphate (meTIMP) and 6-thioguanine nucleotide (6-TGN) concentrations were measured in red blood cells, which is the current practice in clinical monitoring of thiopurines. Enzyme activities were related to metabolite concentrations and clinical characteristics.
resultsA wide range of IMPDH activity was observed both in healthy blood donors (median 13.1, range 4.7-24.2 nmol mg(-1) protein h(-1)) and IBD patients (median 14.0, range 7.0-21.7). There was a negative correlation between IMPDH activity and dose-normalized meTIMP concentrations (r(s) = -0.31, P = 0.03), but no evident correlation to 6-TGN concentration or the meTIMP/6-TGN ratio. There were no significant correlations between TPMT activity and metabolite concentrations.
conclusionEven though the meTIMP concentrations correlated inversely to the IMPDH activity, the role of IMPDH in balancing the formation of methylated and phosphorylated metabolites was not evident. Taken together, the results give cause to question established opinions about thiopurine metabolism.
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