{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:54:10Z","timestamp":1779890050344,"version":"3.53.1"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T00:00:00Z","timestamp":1545955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inosine monophosphate dehydrogenase (IMPDH) is considered as the limiting enzyme of thiopurine metabolism for the formation of 6\u2010thioguanine nucleotides (6\u2010TGN). No data are available on the influence of RBC IMPDH activity on the metabolism of thiopurine drugs in individuals with IBD. The aims of this study were as follows: (a) to carry out a phenotypic study of RBC IMPDH activity in adults and children treated or not with azathioprine (AZA) for autoimmune diseases, and (b) to investigate the relationship between the activities of IMPDH, thiopurine metabolites, inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT). IMPDH activity was determined in 97 adults and 67 children treated or not with AZA. 6\u2010Thioguanine nucleotides (6\u2010TGN), 6\u2010methylmercaptopurine nucleotide (6\u2010MeMPN) levels, and ITPA as well as TPMT activities were measured in RBCs by HPLC. Using the Gaussian mixture model, distribution of IMPDH activity was evaluated. Influence of age, sex and AZA treatment on IMPDH activity was also assessed. A bimodal distribution in IMPDH activity was found with 87% of patients exhibiting normal activity and 13% of patients with high activity. No influence of age, sex and AZA therapy was found. There is no relationship between TPMT, ITPA and IMPDH activities. A negative correlation between IMPDH activity and 6\u2010MeMPN was shown in adults and children (rs\u00a0=\u00a0\u22120.335 <jats:italic>P<\/jats:italic>\u00a0=\u00a00.014 and rs\u00a0=\u00a0\u22120.383 <jats:italic>P<\/jats:italic>\u00a0=\u00a00.012, respectively). Our results suggest that AZA\u2010treated patients exhibiting lower IMPDH activity could have higher Me\u20106MPN levels with higher risk of hepatotoxicity. We demonstrated that RBC matrix could be an interesting alternative to lymphocyte matrix to monitor thiopurine metabolites and enzyme activity.<\/jats:p>","DOI":"10.1111\/bcpt.13176","type":"journal-article","created":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T14:43:51Z","timestamp":1542638631000},"page":"600-606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Red Blood cell IMPDH activity in adults and children with or without azathioprine: Relationship between thiopurine metabolites, ITPA and TPMT activities"],"prefix":"10.1111","volume":"124","author":[{"given":"Antony","family":"Citterio\u2010Quentin","sequence":"first","affiliation":[{"name":"Clinical Pharmacy, Pharmacokinetics and Drug Evaluation Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1 France"},{"name":"Edouard Herriot Hospital, Laboratory of Medical Biology Multisites of University Hospital of Lyon Pharmaco\u2010Toxicology Unit, Hospices Civils de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"El Mahmoudi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy, Pharmacokinetics and Drug Evaluation Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1 France"},{"name":"Edouard Herriot Hospital, Laboratory of Medical Biology Multisites of University Hospital of Lyon Pharmaco\u2010Toxicology Unit, Hospices Civils de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Perret","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy, Pharmacokinetics and Drug Evaluation Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1 France"},{"name":"Edouard Herriot Hospital, Laboratory of Medical Biology Multisites of University Hospital of Lyon Pharmaco\u2010Toxicology Unit, Hospices Civils de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Conway","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy, Pharmacokinetics and Drug Evaluation Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1 France"},{"name":"School of Pharmacy and Pharmaceuticals Sciences Trinity College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishling","family":"Ryan","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy, Pharmacokinetics and Drug Evaluation Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1 France"},{"name":"School of Pharmacy and Pharmaceuticals Sciences Trinity College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Beringer","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy, Pharmacokinetics and Drug Evaluation Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1 France"},{"name":"Edouard Herriot Hospital, Laboratory of Medical Biology Multisites of University Hospital of Lyon Pharmaco\u2010Toxicology Unit, Hospices Civils de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Lachaux","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit H\u00f4pital Femme M\u00e8re Enfant (HFME) Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roselyne","family":"Boulieu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy, Pharmacokinetics and Drug Evaluation Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1 France"},{"name":"Edouard Herriot Hospital, Laboratory of Medical Biology Multisites of University Hospital of Lyon Pharmaco\u2010Toxicology Unit, Hospices Civils de Lyon Lyon 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