pH-Dependent 5-Aminosalicylates Releasing Preparations Do Not Affect Thiopurine Metabolism
pH-Dependent 5-Aminosalicylates Releasing Preparations Do Not Affect Thiopurine Metabolism
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DOI：
10.1159/000495690
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发表时间：
2019-11-01
期刊：
影响因子：
3.2
通讯作者：
Andoh, Akira
中科院分区：
文献类型：
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作者：
Takahashi, Kenichiro;Bamba, Shigeki;Andoh, Akira
背景/目的：硫嘌呤是维持治疗炎症性肠病(IBD)的关键药物。时间依赖的5-氨基水杨酸酯(5-ASA)释放制剂(时间依赖的5-ASA)增加硫嘌呤的活性代谢物6-硫代鸟嘌呤核苷酸(6-TGN)。然而，pH依赖型5-ASA释放制剂(pH依赖型5-ASA)对硫嘌呤代谢的影响尚未见报道。方法：对134例接受硫代嘌呤治疗的IBD患者进行回顾性研究。包括服用相同剂量的硫代嘌呤制剂至少28天后的6-甲硫基嘌呤(6-MMPs)/6-TGN值。结果：时间依赖性5-ASA组的6-MMP6-TGN比值明显低于不含5-ASA组和pH依赖性5-ASA组(p分别为0.008和0.001)。Spearman等级相关系数显示，呈时间依赖性的5-AsA日剂量与6-MMP6-TGN比值呈负相关(r=-0.362，p=0.003)。对6-MMP6-TGN比值为1或以上且小于1的患者进行多因素Logistic回归分析。使用时间依赖性的5-AsA和伴随的别嘌醇对独立的6-MMP6-TGN比值产生负面影响(p分别为0.006和0.007)。结论：5-ASA可降低6-MMP6-TGN的比例，但不依赖于pH，而具有时间依赖性。我们还证实了伴随的别嘌醇导致了较低的6-MMP6-TGN比率。(C)2019年S.Karger AG，巴塞尔
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