title: Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors: Gastroenterology Division, A.O. Ordine Mauriziano, Torino, Italy. mdaperno@tele2.it
authors: M
authors: M
authors: Daperno
authors: R
authors: R
authors: Sostegni
authors: R
authors: R
authors: Canaparo
authors: L
authors: L
authors: Serpe
authors: A
authors: A
authors: Lavagna
authors: L
authors: L
authors: Crocellà
authors: F
authors: F
authors: Castagno
authors: A
authors: A
authors: Vernetto
authors: C
authors: C
authors: Rigazio
authors: E
authors: E
authors: Ercole
authors: S
authors: S
authors: D'Antico
authors: A
authors: A
authors: Pera
authors: G
authors: G
authors: Zara
authors: R
authors: R
authors: Rocca
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001379:Azathioprine / Q000009:adverse effects*; D004247:DNA / Q000235:genetics; D004347:Drug Interactions / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects*; D019804:Mesalamine / Q000009:adverse effects*; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D019804:Mesalamine; D004247:DNA; D015122:Mercaptopurine; D001379:Azathioprine