期刊
DIGESTION
卷 100, 期 4, 页码 238-246出版社
KARGER
DOI: 10.1159/000495690
关键词
Mesalazine; Crohn's disease; Ulcerative colitis
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [18K08002, 18K07938, 18K10990, 16K09308, 16K9846, 18K07909]
- Ministry of Health, Labor and Welfare of Japan [067]
- Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED [15AeK0109047h0002]
- Smoking Research Foundation [1848]
- Grants-in-Aid for Scientific Research [16K09308, 18K07938, 18K07909, 18K10990] Funding Source: KAKEN
Background/Aims: Thiopurines are key drugs in maintenance therapy for treating inflammatory bowel disease (IBD). Time-dependent 5-aminosalicylates (5-ASA) releasing preparations (time-dependent 5-ASA) increase 6-thioguanine nucleotide (6-TGN), an active metabolite of thiopurines. However, the effects of pH-dependent 5-ASA releasing preparations (pH-dependent 5-ASA) on thiopurine metabolism were not reported. Methods: We conducted a retrospective study of 134 IBD patients who received thiopurine treatment. The 6-methylmercaptopurine (6-MMP)/6-TGN values after taking the same dose of thiopurine preparations for at least 28 days were included. Results: There was a significant decrease in the 6-MMP/6-TGN ratio in time-dependent 5-ASA compared with group without 5-ASA preparations and the pH-dependent 5-ASA group (p = 0.008 and < 0.001 respectively). Spearman's rank correlation coefficient indicated a negative relationship between the daily oral dose of time-dependent 5-ASA and the 6-MMP/6-TGN ratio (r = -0.362, p = 0.003). Multivariate logistic regression analysis was performed in the groups with 6-MMP/6-TGN ratios of 1 or more and less than 1. The use of time-dependent 5-ASA and concomitant allopurinol negatively affected the independent 6-MMP/6-TGN ratio (p = 0.006 and 0.007 respectively). Conclusion: Our study revealed that time-dependent but not pH-dependent 5-ASA decreases the 6-MMP/6-TGN ratio. We also confirmed that concomitant allopurinol results in a low 6-MMP/6TGN ratio. (C) 2019 S. Karger AG, Basel
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