Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease

Autor:	Roberto Canaparo, Franco Castagno, Alessandro Lavagna, Sergio D'Antico, Rodolfo Rocca, Elena Ercole, A. Vernetto, L. Crocellà, Marco Daperno, Loredana Serpe, G. P. Zara, C. Rigazio, R. Sostegni, Angelo Pera
Rok vydání:	2009
Předmět:	Adult Male Drug medicine.medical_specialty Genotype media_common.quotation_subject Polymerase Chain Reaction Inflammatory bowel disease Gastroenterology Young Adult Pharmacokinetics Internal medicine Azathioprine Humans Medicine Drug Interactions Pharmacology (medical) Prospective Studies Mesalamine Prospective cohort study media_common Hepatology Thiopurine methyltransferase biology Mercaptopurine business.industry Anti-Inflammatory Agents Non-Steroidal DNA Metabolism Middle Aged Inflammatory Bowel Diseases medicine.disease Ulcerative colitis Concomitant Multivariate Analysis biology.protein Female business Immunosuppressive Agents
Zdroj:	Alimentary Pharmacology & Therapeutics. 30:843-853
ISSN:	1365-2036 0269-2813
Popis:	Aliment Pharmacol Ther 30, 843–853 Summary Background Thiopurines are increasingly used in the treatment of inflammatory bowel disease (IBD), being the most common immunosuppressive therapy; however, potentially harmful interactions between thiopurines and other drugs (especially 5-aminosalicylic acid, 5-ASA) were described. Aim To explore potential interactions between thiopurines and concomitant medications. Methods A total of 183 consecutive IBD patients were enrolled. Clinical characteristics and concomitant medications were recorded. Thiopurine metabolism was analysed with thiopurine S-methyl transferase (TPMT) genetic variants and enzyme activity assays. Comparisons were carried out with stratification of patients according to clinical characteristics and active treatments. Results Based on TPMT genetics, 95% IBD patients were wild-type homozygous, the remaining being heterozygous. Median TPMT activity was 24.9 U/Hgb g (IQR 20.7–29.5). No difference in TPMT activity was noted according to 5-ASA exposure. IBD patients on thiopurines had higher TPMT activity levels, but no dose-effect was evident. No difference in TPMT activity was observed in 41 (63%) patients co-treated with 5-ASA. In patients on active thiopurines also, 6-TGN and 6-MMP levels were evaluated and no significant difference was observed based on co-medication. TPMT activity was independently associated only with thiopurines dose (P = 0.016). Conclusions Our data suggest the absence of significant interactions between thiopurines and 5-ASA.
Databáze:	OpenAIRE
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