Comparison of Effects on 6-Thioguanine Nucleotides According to Mesalazine Formulation in Pediatric Patients with Ulcerative Colitis

Purpose: Mesalazine and thiopurines are important therapeutic agents for pediatric patients with ulcerative colitis (UC). Mesalazine, which may be administered in different forms depending on delivery mechanisms, can affect thiopurine metabolism, leading to increased 6-thioguanine nucleotides (6-TGN) levels. Therefore, when using these two drugs simultaneously, their interactions must be considered. This study aimed to analyze 6-TGN according to mesalazine formulation in pediatric patients with UC. Methods: We retrospectively reviewed the data of 236 pediatric patients with UC who visited a single health center between January 2021 and December 2023. Among the enrolled patients, 198 were administered thiopurines, and of these, 136 underwent testing for 6-TGN. Findings: The mean dose of azathioprine (AZA) was 0.66 mg/kg, and the mean 6-TGN level was 211.64 pmol/8 × 10^8 red blood cells (RBCs). The mean 6-TGN level for the group concurrently using time-dependent mesalazine and AZA was 245.00 pmol/8 × 10^8 RBCs, while that for the group concurrently using multimatrix mesalazine (MMX) and AZA was 141.97 pmol/8 × 10^8 RBCs (P < 0.001). In the same patients, the mean 6-TGN level during time-dependent mesalazine treatment was 290.34 pmol/8 × 108 RBCs, whereas the mean 6-TGN level measured after switching to MMX was 148.54 pmol/8 × 108 RBCs (P = 0.016). Implications: The group treated with MMX and AZA had a lower mean 6-TGN level than the group treated with time-dependent mesalazine and AZA. The mean 6-TGN level significantly decreased after switching from time-dependent mesalazine to MMX in the same patients. Therefore, when administering MMX, a higher dose of AZA is necessary to reach the target 6-TGN level, compared to the dose required when using time-dependent mesalazine.