Dewit O
St. Luc University Hospital, Department of Gastroenterology, Brussels, Belgium.
Acta Gastroenterol Belg. 2010 Jul-Sep;73(3):331-5.
Thiopurines (TP) are widely used in the management of inflammatory bowel diseases. Side-effects and inefficacy are a major concern as they lead to withdrawal of the drug. Tools investigating TP metabolism are useful to avoid inadequate cessation of TP therapy. TP metabolism is complex and many enzymes are involved. Among them, Thiopurine methyltransferase (TPMT) is the only one routinely measured by pheno- or genotyping. In this review, the rationale for TPMT and thiopurine metabolites, 6-thioguanine nucleotides and 6-methylmercaptopurine, determination in clinical practice is discussed, specifically in case of thiopurine failure and recommendations are given about their interpretation and potential dose optimization of TP drugs.
硫嘌呤（TP）广泛用于炎症性肠病的治疗。副作用和无效是一个主要问题，因为它们会导致停药。研究TP代谢的工具有助于避免TP治疗的不当停药。TP代谢复杂，涉及多种酶。其中，硫嘌呤甲基转移酶（TPMT）是唯一通过表型或基因分型进行常规检测的酶。在本综述中，讨论了在临床实践中测定TPMT和硫嘌呤代谢物（6-硫鸟嘌呤核苷酸和6-甲基巯基嘌呤）的基本原理，特别是在硫嘌呤治疗失败的情况下，并给出了关于它们的解释以及TP药物潜在剂量优化的建议。
