5-aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine.
Inflamm Bowel Dis
; 12(4): 251-7, 2006 Apr.
Article
em En
| MEDLINE
| ID: mdl-16633046
ABSTRACT
BACKGROUND:
Small uncontrolled trials have suggested that 5-aminosalicylate (5-ASA) medications increase 6-thioguanine nucleotide (6-TGn) levels in adults with Crohn's disease (CD) on azathioprine (AZA) or 6-mercaptopurine (6-MP), presumably through the inhibition of thiopurine methyltransferase (TPMT). We tested the theory that coadministration of 5-ASA agents with AZA/6-MP results in higher 6-TGn levels in a large cohort of children and adults with CD or ulcerative colitis (UC).METHODS:
A retrospective cohort study identified all children and adults treated for IBD with AZA/6-MP at 2 tertiary medical centers. Patients were included if their TPMT genotype was known and 6-TGn and 6-methymercaptopurine (6-MMP) levels had been obtained after 3 months of clinical remission at a stable dose of AZA/6-MP. 6-TGn and 6-MMP levels were compared between patients taking and those not taking 5-ASA medications through the use of linear regression models to identify and adjust for potentially confounding variables.RESULTS:
Of the 126 patients included, 88 were taking 5-ASA medications. Patients on 5-ASA agents had higher mean 6-TGn levels after adjustment for confounding variables (Delta6-TGn, 47.6 +/- 21.8 pmol/8 x 10 red blood cells; P = 0.03). CD and TPMT heterozygosity was independently associated with higher 6-TGn levels (P = 0.01 and P = 0.03, respectively). 5-ASA exposure was not associated with a change in 6-MMP levels.CONCLUSIONS:
We found that 5-ASA therapy is associated with higher 6-TGn levels in children and adults with IBD on 6-MP/AZA. TPMT inhibition may not explain this effect because 5-ASA exposure did not affect 6-MMP levels. The observed association of CD with higher 6-TGn levels is novel and needs to be verified in prospective studies.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Azatioprina
/
Tioguanina
/
Doenças Inflamatórias Intestinais
/
Anti-Inflamatórios não Esteroides
/
Mesalamina
/
Imunossupressores
/
Mercaptopurina
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Inflamm Bowel Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos