Therapeutic Agents and Patient Characteristics Affecting Metabolism of Thiopurines in Patients with Inflammatory Bowel Disease.

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.