Background And Aim: There have been no reports on 6-thioguanine nucleotide (6-TGN) concentrations in Japanese patients with inflammatory bowel disease (IBD) undergoing azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy. The aim of this study was to assess 6-TGN concentrations in Japanese IBD patients.
Methods: Eighty-three patients with Crohn's disease (n = 42) and ulcerative colitis (n = 41) were enrolled. In 69 patients, AZA was prescribed at 50 mg/day, and seven patients were given 75 (n = 5) or 100 mg/day (n = 2). 6-MP was administered at 30 mg/day (n = 7). The 6-TGN concentrations were then assayed by high-performance liquid chromatography.
Results: The mean 6-TGN concentrations of the entire study population (n = 83) were 277.9 +/- 179.8 pmol/8 x 10(8) red blood cells (RBC). The mean 6-TGN concentrations in those patients with active disease (n = 38) and those in remission (n = 45) were 232.9 +/- 159.7(mean +/- SD) and 342.8 +/- 184.6 pmol/8 x 10(8) RBC, respectively (P < 0.05). The odds ratio of being in remission and having a 6-TGN value >235 pmol/8 x 10(8) RBC was 2.6 (95% CI 1.05-6.2). A significant inverse correlation was found between the white blood cell (WBC) counts and 6-TGN concentrations (r = -0.301, P < 0.05, n = 83); the mean WBC counts of the active patients (6780 +/- 2412) were significantly higher than the patients in clinical remission (5468 +/- 1920, P < 0.05). Three patients with severe leukopenia and 10 patients with high 6-TGN concentrations had no thiopurine S-methyl transferase mutations.
Conclusion: The 6-TGN concentrations in Japanese patients with IBD on low-dose AZA and 6-MP therapy were comparable to those reported from Western countries. The monitoring of 6-TGN concentrations may be helpful for developing a therapeutic strategy for Japanese IBD patients.
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http://dx.doi.org/10.1111/j.1440-1746.2008.05419.x | DOI Listing |
Fukushima J Med Sci
December 2024
Department of Coloproctology and Gastroenterology, Aizu Medical Center Fukushima Medical University.
Objectives: In inflammatory bowel disease therapy, thiopurines have been essential. However, several reports have investigated factors affecting thiopurine metabolism to date. This study investigated factors affecting intracellular concentrations of 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) in a real-world setting.
View Article and Find Full Text PDFPharmacogenomics
October 2024
Laboratory of Pharmacology, University Hospital of Monastir, Faculty of Medicine, University of Monastir, Tunisia.
Br J Clin Pharmacol
December 2024
Department of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, Netherlands.
Aims: Conventional thiopurines (azathioprine and mercaptopurine) remain standard therapy to maintain steroid sparing remission in inflammatory bowel disease (IBD), but are regularly discontinued due to adverse drug reactions (ADRs). Measurement of the metabolites 6-thioguanine nucleotides (6-TGN), 6-methylmercaptopurine ribonucleotides (6-MMPR) and the 6-MMPR/6-TGN ratio, may predict the development of these ADRs. Our aim was to evaluate whether early thiopurine metabolite measurements were associated with clinical outcomes.
View Article and Find Full Text PDFClin Pharmacokinet
August 2024
Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Lupus Sci Med
January 2024
Department of Medicine, Duke University, Durham, North Carolina, USA.
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