Differences Between Children and Adults in Thiopurine Methyltransferase Activity and Metabolite Formation During Thiopurine Therapy: Possible Role of Concomitant Methotrexate
Differences Between Children and Adults in Thiopurine Methyltransferase Activity and Metabolite Formation During Thiopurine Therapy: Possible Role of Concomitant Methotrexate
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硫嘌呤治疗期间儿童和成人硫嘌呤甲基转移酶活性和代谢物形成的差异：联合甲氨蝶呤的可能作用
DOI：
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发表时间：
2002
影响因子：
2.5
通讯作者：
C. Peterson
中科院分区：
文献类型：
--
作者：
B. Pettersson;S. Almér;F. Albertioni;S. Söderhäll;C. Peterson
本研究旨在探讨硫嘌呤甲基转移酶（TPMT）多态性在硫唑嘌呤和6-巯基嘌呤治疗炎症性肠病和儿童白血病的代谢和临床效果中的作用。目前的假设是，硫嘌呤的细胞毒性作用是由硫鸟嘌呤核苷酸掺入DNA引起的。在这种情况下，TPMT催化的S-甲基化可以被视为竞争代谢途径。作者分析了122例接受硫唑嘌呤或6-巯基嘌呤治疗的患者（83例成人炎症性肠病和39例儿童急性淋巴细胞白血病）和290例未经治疗的对照组（219例成人献血者和71例儿童）的红细胞中TPMT活性。还测定了患者红细胞中硫鸟嘌呤核苷酸和甲硫肌苷一磷酸的浓度。TPMT活性和甲基硫代肌苷酸和硫代鸟嘌呤核苷酸的浓度在儿童高于成人。除成人患者外，所有儿童患者均接受甲氨蝶呤伴随治疗。甲氨蝶呤和6-巯基嘌呤之间的相互作用已被描述，并可能解释的结果。炎症性肠病成人患者TPMT活性低与药物不良反应发生率增加相关。然而，TPMT活性和甲基硫代肌苷单磷酸或硫代鸟嘌呤核苷酸的红细胞浓度之间，或这些代谢产物的浓度和不良反应的发生之间没有相关性。结果表明，巯基嘌呤代谢对药物作用的作用是复杂的。
This study examined the role of thiopurine methyltransferase (TPMT) polymorphism in the metabolism and clinical effects of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease and childhood leukemia. The current hypothesis is that the cytotoxic effects of thiopurines are caused by the incorporation of thioguanine nucleotides into DNA. In this context, S-methylation catalyzed by TPMT can be regarded as a competing metabolic pathway. The authors assayed the TPMT activity in red blood cells from 122 patients treated with azathioprine or 6-mercaptopurine (83 adults with inflammatory bowel disease and 39 children with acute lymphoblastic leukemia) and in 290 untreated controls (219 adult blood donors and 71 children). The concentrations of thioguanine nucleotides and methylthioinosine monophosphate were also assayed in red blood cells from the patients. The TPMT activity and the concentrations of methylthioinosine monophosphate and thioguanine nucleotides were higher in children than in adults. All children but no adult patient received concomitant methotrexate. Interaction between methotrexate and 6-mercaptopurine has been described, and may explain the results. Low TPMT activity in adult patients with inflammatory bowel disease correlated to an increased incidence of adverse drug reactions. However, there was no correlation between TPMT activity and the red blood cell concentrations of methylthioinosine monophosphate or thioguanine nucleotides, or between the concentrations of these metabolites and the occurrence of adverse effects. The results show that the role of thiopurine metabolism for drug effects is complex.
人肝硫嘌呤甲基转移酶药物遗传学：生化特性、肝-红细胞相关性和同工酶的存在。
DOI：
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发表时间：
1992
期刊：
Pharmacogenetics
影响因子：
--
作者：
Szumlanski,CL;Honchel,R;Scott,MC;Weinshilboum,RM
通讯作者：
Weinshilboum,RM
影响因子：
3.1
作者：
Szumlanski, C;Otterness, D;Weinshilboum, R
通讯作者：
Weinshilboum, R
红细胞中的多态硫嘌呤甲基转移酶表明患有急性淋巴细胞白血病的儿童的白血病母细胞具有活性。
影响因子：
20.3
作者：
McLeod,HL;Relling,MV;Liu,Q;Pui,CH;Evans,WE
通讯作者：
Evans,WE