Seidman Ernest G
Division of Gastroenterology, Hepatology, and Nutrition, Faculty of Medicine, University of Montreal, Montreal, Canada.
Rev Gastroenterol Disord. 2003;3 Suppl 1:S30-8.
6-mercaptopurine (6-MP) and its parent drug azathioprine (AZA) have been proven to be effective for both steroid-dependent and chronically active, or steroid-resistant inflammatory bowel disease, as well as for the prevention of relapse. Concerns about toxicity, delayed onset of action, and therapeutic failure (1 out of 3 patients) have restricted their use. Recent pharmacogenetic advances have led to the development of novel strategies to optimize and individualize therapy with AZA and 6-MP, maximizing efficacy while minimizing toxicity. We have defined a range of optimal therapeutic 6-MP metabolite levels, as well as an association of metabolite levels with medication-induced toxicity and the genotype of the main catabolic enzyme, thiopurine methyltransferase (TPMT). Measurement of 6-MP metabolite levels and TPMT molecular analysis provide clinicians with useful tools for optimizing therapeutic response to 6-MP/AZA, as well as for identifying individuals at increased risk for drug-induced toxicity.
6-巯基嘌呤（6-MP）及其母体药物硫唑嘌呤（AZA）已被证明对激素依赖型、慢性活动型或激素抵抗型炎症性肠病以及预防复发均有效。然而，对毒性、起效延迟和治疗失败（三分之一的患者）的担忧限制了它们的使用。近期药物遗传学的进展促使了新策略的发展，以优化和个体化使用AZA和6-MP的治疗，在将毒性降至最低的同时最大化疗效。我们已经确定了一系列最佳治疗性6-MP代谢物水平，以及代谢物水平与药物诱导毒性和主要分解代谢酶硫嘌呤甲基转移酶（TPMT）基因型之间的关联。测量6-MP代谢物水平和TPMT分子分析为临床医生提供了有用的工具，用于优化对6-MP/AZA的治疗反应，以及识别药物诱导毒性风险增加的个体。
