| Abstrakt: |
Background: Genetic polymorphisms in thiopurine methyltransferase (TPMT) influence the metabolism of azathioprine (AZA) and 6-mercaptopurine (6-MP) in patients with inflammatory bowel disease (IBD).Objective: The aim of this study is to assess the relationship between TPMT activity and 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine ribonucleotide (6-MMPN) levels in patients with IBD in clinical practice.Methods: TPMT activity, 6-TGN levels, and 6-MMPN levels were analyzed in all patients who had a TPMT assessment and at least 2 metabolite profiles sent to Prometheus Laboratories Inc. (San Diego, CA) from June 2000 to February 2004. The use of AZA or 6-MP and the dosing of the drug were at the discretion of the patient's gastroenterologist. Linear regression was used to analyze the relationships between TPMT and 6-TGN, 6-MMPN, and 6-MMPN/6-TGN.Results: A total of 1,021 patients were identified. Linear regression showed a significant inverse relationship between TPMT activity and 6-TGN level, r(1017)=--0.162, P<0.01, a significant direct relationship between TPMT activity and 6-MMPN level, r(1018)=0.172, P<0.01, and a significant direct relationship between TPMT activity and 6-MMPN/6-TGN ratio, r(589)=0.141, P<0.01.Conclusions: Higher TPMT activity is associated with lower 6-TGN levels and higher 6-MMPN levels in patients with IBD who were treated with AZA or 6-MP in clinical practice. [ABSTRACT FROM AUTHOR] |
