pH-Dependent 5-Aminosalicylates Releasing Preparations Do Not Affect Thiopurine Metabolism

被引:4
|
作者
Takahashi, Kenichiro [1 ]
Bamba, Shigeki [2 ]
Morita, Yasuhiro [1 ]
Nishida, Atsushi [1 ]
Kawahara, Masahiro [1 ]
Inatomi, Osamu [1 ]
Sugimoto, Mitsushige [3 ]
Sasaki, Masaya [2 ]
Andoh, Akira [1 ]
机构
[1] Shiga Univ Med Sci, Dept Med, Otsu, Shiga, Japan
[2] Shiga Univ Med Sci, Div Clin Nutr, Otsu, Shiga 5202192, Japan
[3] Shiga Univ Med Sci, Div Digest Endoscopy, Otsu, Shiga, Japan
关键词
Mesalazine; Crohn's disease; Ulcerative colitis; INFLAMMATORY-BOWEL-DISEASE; INOSINE TRIPHOSPHATE PYROPHOSPHATASE; ADVERSE DRUG-REACTIONS; S-METHYLTRANSFERASE; JAPANESE PATIENTS; CROHNS-DISEASE; AZATHIOPRINE; THERAPY; 6-THIOGUANINE; ALLOPURINOL;
D O I
10.1159/000495690
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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
引用
收藏
页码:238 / 246
页数:9
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