Semmelweis University, 2nd Department of Medicine, Budapest, Koranyi, Hungary.
Expert Opin Drug Metab Toxicol. 2010 Dec;6(12):1505-14. doi: 10.1517/17425255.2010.525505. Epub 2010 Oct 5.
traditional immunosuppressants, including azathioprine, remain the mainstay of therapy in steroid dependent/refractory patients with inflammatory bowel diseases (IBD). The main limitations of its use are its side effects appearing in about a fifth of the patients, including myelosuppression and liver toxicity. Major complications occur in patients with low thiopurine-S-methyltransferase (TPMT) enzyme activity; however, the clinical relevance of these tests remains conflictive.
in this review, the authors aim to summarize the new data regarding the relationship between the pharmacology of thiopurines and pathogenesis of adverse events.
readers will gain an understanding of the metabolism of thiopurines, side effect profile, pharmacological background of side effects, importance of metabolite monitoring, clinical relevance of inherited differences in drug metabolism and other conditions (e.g., concomitant use of allopurinol) which can modify enzyme activity. By gaining an understanding of the pharmacology and metabolism of thiopurines, clinicians will be able to optimize thiopurine therapy in IBD.
TPMT testing and metabolite monitoring are still not considered the standard of care, and clinicians will continue to choose the approach that best suits their clinical practice and patient needs. Regardless of what strategy is chosen, patients need to be carefully monitored and well informed about the potential risks.
包括硫唑嘌呤在内的传统免疫抑制剂仍然是类固醇依赖/难治性炎症性肠病（IBD）患者治疗的主要方法。其使用的主要限制是约五分之一的患者会出现副作用，包括骨髓抑制和肝毒性。低硫嘌呤 S-甲基转移酶（TPMT）酶活性的患者会发生严重并发症；然而，这些检测的临床相关性仍然存在争议。
在这篇综述中，作者旨在总结关于硫嘌呤的药理学与不良反应发病机制之间关系的新数据。
读者将了解硫嘌呤的代谢、副作用概况、副作用的药理学背景、代谢物监测的重要性、药物代谢遗传差异的临床相关性以及其他可改变酶活性的情况（例如，别嘌醇的同时使用）。通过了解硫嘌呤的药理学和代谢，临床医生将能够优化 IBD 中的硫嘌呤治疗。
TPMT 检测和代谢物监测仍不被视为标准治疗方法，临床医生将继续选择最适合其临床实践和患者需求的方法。无论选择哪种策略，都需要仔细监测患者并使其充分了解潜在风险。
