title: The role of thiopurine metabolites in inflammatory bowel disease and rheumatological disorders.
abstract: Thiopurines have been a cornerstone of medical management of patients with inflammatory bowel disease(IBD) and many rheumatological disorders. The thiopurines are metabolized to their end products, 6-methymercaptopurine (6MMP) and the 6-thioguanine nucleotides (6TGN), with 6TGN being responsible for thiopurine efficacy by causing apoptosis and preventing activation and proliferation of T-lymphocytes. In IBD, conventional weight-based dosing with thiopurines leads to an inadequate response in many patients. Utilizing measurement of these metabolites and then employing dose optimization strategies has led to markedly improved outcomes in IBD. Switching between thiopurines as well as the addition of low-dose allopurinol can overcome adverse events and elevate 6TGN levels into the therapeutic window. There is a paucity of data on thiopurine metabolites in rheumatological diseases and further research is required.
authors.forename: Antony B
authors.initials: AB
authors.lastname: Friedman
authors.forename: Miles P
authors.initials: MP
authors.lastname: Sparrow
authors.forename: Peter R
authors.initials: PR
authors.lastname: Gibson
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D004347:Drug Interactions; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D011355:Prodrugs / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D011687:Purines / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000276:immunology; D013872:Thionucleosides / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D011355:Prodrugs; D011687:Purines; D013872:Thionucleosides; D001379:Azathioprine