Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease
Article first published online: 24 JUL 2009
© 2009 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 30, Issue 8, pages 843–853, October 2009
How to Cite
DAPERNO, M., SOSTEGNI, R., CANAPARO, R., SERPE, L., LAVAGNA, A., CROCELLÀ, L., CASTAGNO, F., VERNETTO, A., RIGAZIO, C., ERCOLE, E., D’ANTICO, S., PERA, A., ZARA, G. and ROCCA, R. (2009), Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease. Alimentary Pharmacology & Therapeutics, 30: 843–853. doi: 10.1111/j.1365-2036.2009.04106.x
- Issue published online: 16 SEP 2009
- Article first published online: 24 JUL 2009
- Publication data Submitted 20 March 2009 First decision 26 April 2009 Resumitted 22 July 2009 Accepted 22 July 2009 Epub Accepted Article 24 July 2009
Aliment Pharmacol Ther 30, 843–853
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.