FUKUSHIMA JOURNAL OF MEDICAL SCIENCE
Online ISSN : 2185-4610
Print ISSN : 0016-2590
ISSN-L : 0016-2590
Original article
Therapeutic Agents and Patient Characteristics Affecting Metabolism of Thiopurines in Patients with Inflammatory Bowel Disease
Masato Aizawa, Kohei Suzuki, Yuki Nakajima, Kenichi Utano, Kana Tamazawa, Kenta Ueda, Jun Wada, Kentaro Sato, Goro Shibukawa, Noriko Tanaka, Kazutomo Togashi
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2025 Volume 71 Issue 1 Pages 47-55

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Abstract

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.

Methods: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.

Results: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.

Conclusions:Patients who received allopurinol, a high dose of thiopurine, or were female showed higher 6-TGN levels.

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© 2025 The Fukushima Society of Medical Science

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