Introduction. Thiopurines, such as azathioprine (AZA) and 6-mercaptopurine (6-MP), are immunomodulatory agents, used for the maintenance of remission in children with inflammatory bowel disease (IBD)—Crohn’s disease (CD) and ulcerative colitis (UC), as well as with autoimmunological hepatitis (AIH). Measurements of thiopurine metabolites may allow identifying patients at risk for toxicity and nonadherence. It can also provide an explanation for the ineffectiveness of the treatment, observed in some patients. Patients and Methods. A retrospective analysis was carried out of sixty-eight patients (thirty-six patients with CD, eighteen with UC, and fourteen with AIH), treated with AZA. Thiopurine metabolites, 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP), were assayed by high-performance liquid chromatography (HPLC), and the AZA dose was adjusted when 6-TGN concentration was known. Result. Only twenty-five (41%) children had therapeutic 6-TGN concentrations, ten (16%) subjects had suboptimal 6-TGN concentrations, and twenty-six subjects (43%) had 6-TGN concentrations above the recommended therapeutic range. 6-MMP was not above the therapeutic range in any case. Seven subjects revealed undetectable 6-TGN and 6-MMP levels, indicating nonadherence. The mean AZA dose after the 6-TGN concentration-related adjustment did not differ, in comparison to the initial dose, either in IBD or AIH groups. The mean AZA dose was lower in AIH than in IBD. The subjects with an optimal 6-TGN level presented with a higher ratio of remission (88%) than the under- or overdosed patients (60% and 69%), respectively (, ). Conclusion. Timely measurements of thiopurine metabolites can be a useful tool to identify nonadherent patients before a decision is taken to switch to another drug. We may also spot the patients who receive either too low or too high doses, compensating dose deviations in an appropriate way. The patients with optimal 6-TGN levels presented a higher percentage of remission than the under- or overdosed patients. In most patients, both initial and adjusted AZA doses, lower than suggested in guidelines, appeared to be sufficient to maintain remission.

中文翻译：

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测定硫唑嘌呤治疗炎症性肠病和自身免疫性肝炎儿童硫嘌呤代谢物的有用性

介绍。硫嘌呤，如硫唑嘌呤 (AZA) 和 6-巯基嘌呤 (6-MP)，是免疫调节剂，用于维持炎症性肠病 (IBD)——克罗恩病 (CD) 和溃疡性结肠炎 (UC) 患儿的缓解，以及自身免疫性肝炎 (AIH)。硫嘌呤代谢物的测量可能允许识别有毒性和不依从性风险的患者。它还可以解释在某些患者中观察到的治疗无效。患者和方法. 对 68 名接受 AZA 治疗的患者（36 名 CD 患者、18 名 UC 患者和 14 名 AIH 患者）进行了回顾性分析。硫嘌呤代谢物 6-硫鸟嘌呤核苷酸 (6-TGN) 和 6-甲基巯基嘌呤 (6-MMP) 通过高效液相色谱 (HPLC) 进行测定，当 6-TGN 浓度已知时，调整 AZA 剂量。结果. 只有二​​十五名 (41%) 儿童的 6-TGN 浓度具有治疗性，十名 (16%) 受试者的 6-TGN 浓度不理想，二十六名 (43%) 受试者的 6-TGN 浓度高于推荐的治疗范围。在任何情况下，6-MMP 都不超过治疗范围。七名受试者显示检测不到 6-TGN 和 6-MMP 水平，表明不依从。与初始剂量相比，IBD 或 AIH 组中 6-TGN 浓度相关调整后的平均 AZA 剂量没有差异。AIH 患者的平均 AZA 剂量低于 IBD。具有最佳 6-TGN 水平的受试者的缓解率 (88%) 分别高于剂量不足或过量的患者 (60% 和 69%)。, ）。 结论。在决定改用另一种药物之前，及时测量硫嘌呤代谢物是识别不依从患者的有用工具。我们还可以发现接受过低或过高剂量的患者，以适当的方式补偿剂量偏差。与剂量不足或过量的患者相比，具有最佳 6-TGN 水平的患者表现出更高的缓解百分比。在大多数患者中，初始和调整后的 AZA 剂量（低于指南中建议的剂量）似乎足以维持缓解。