Aizawa Masato, Suzuki Kohei, Nakajima Yuki, Utano Kenichi, Tamazawa Kana, Ueda Kenta, Wada Jun, Sato Kentaro, Shibukawa Goro, Tanaka Noriko, Togashi Kazutomo
Department of Coloproctology and Gastroenterology, Aizu Medical Center Fukushima Medical University.
Health Data Science Research Section, Tokyo Metropolitan Institute of Gerontology.
Fukushima J Med Sci. 2025 Jan 18;71(1):47-55. doi: 10.5387/fms.24-00009. Epub 2025 Jan 7.
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.
Between May 2013 and October 2021 in one institution, 44 patients (median age 44 years;male 35, female 9;ulcerative colitis 32, Crohn's disease 12) receiving thiopurines were reviewed. Intracellular 6-TGN/6-MMP concentrations were measured by high-performance liquid chromatography, and the initial measurement in each patient was used for the study.
The 6-TGN level was significantly higher in females, with mild disease activity, absence of NUDT15 polymorphism, and allopurinol administration. A higher trend was observed with high thiopurine dosage (>50 mg). 6-MMP levels were significantly lower with concomitant use of time-dependent 5-aminosalicylic acid (5-ASA) and allopurinol, and higher with high thiopurine dosage. On multivariate analysis of variance, logarithmically transformed 6-TGN levels were significantly higher in females, with high thiopurine dosage, and allopurinol administration. Similarly, logarithmically transformed 6-MMP levels were significantly higher with time-dependent 5-ASA administration and high thiopurine dosage.
Patients who received allopurinol, a high dose of thiopurine, or were female showed higher 6-TGN levels.
在炎症性肠病治疗中，硫唑嘌呤一直至关重要。然而，迄今为止已有多项报告对影响硫唑嘌呤代谢的因素进行了研究。本研究在实际临床环境中调查了影响6-硫鸟嘌呤核苷酸（6-TGN）和6-甲基巯基嘌呤（6-MMP）细胞内浓度的因素。
2013年5月至2021年10月期间，对某机构中44例接受硫唑嘌呤治疗的患者（中位年龄44岁；男性35例，女性9例；溃疡性结肠炎32例，克罗恩病12例）进行了回顾性分析。通过高效液相色谱法测量细胞内6-TGN/6-MMP浓度，并将每位患者的首次测量结果用于本研究。
女性、疾病活动度较轻、不存在NUDT15基因多态性以及使用别嘌醇的患者，其6-TGN水平显著更高。硫唑嘌呤高剂量（>50 mg）时观察到更高的趋势。同时使用时间依赖性5-氨基水杨酸（5-ASA）和别嘌醇时，6-MMP水平显著更低，而硫唑嘌呤高剂量时则更高。在多变量方差分析中，对数转换后的6-TGN水平在女性、硫唑嘌呤高剂量以及使用别嘌醇的患者中显著更高。同样，对数转换后的6-MMP水平在使用时间依赖性5-ASA和硫唑嘌呤高剂量时显著更高。
接受别嘌醇、高剂量硫唑嘌呤治疗的患者或女性患者的6-TGN水平更高。
