Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease.
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.
Daperno
M
M
Gastroenterology Division, A.O. Ordine Mauriziano, Torino, Italy. mdaperno@tele2.it
Sostegni
R
R
Canaparo
R
R
Serpe
L
L
Lavagna
A
A
Crocellà
L
L
Castagno
F
F
Vernetto
A
A
Rigazio
C
C
Ercole
E
E
D'Antico
S
S
Pera
A
A
Zara
G
G
Rocca
R
R
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D019804:Mesalamine; D004247:DNA; D015122:Mercaptopurine; D001379:Azathioprine