An integrated triple approach - TPMT phenotype, NUDT-15 genotype, and therapeutic drug monitoring of thiopurine metabolites for optimal clinical efficacy: a case series.
Silvia Joseph, Ratna Prabha, David Mathew Thomas, A J Joseph
{"title":"An integrated triple approach - TPMT phenotype, NUDT-15 genotype, and therapeutic drug monitoring of thiopurine metabolites for optimal clinical efficacy: a case series.","authors":"Silvia Joseph, Ratna Prabha, David Mathew Thomas, A J Joseph","doi":"10.1080/17410541.2026.2657977","DOIUrl":null,"url":null,"abstract":"<p><p>Thiopurines, a widely used immunosuppressant for autoimmune and inflammatory condition, is associated with potentially severe adverse effects, particularly myelosuppression. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) can largely predict the risk of thiopurine-induced toxicity. Therapeutic drug monitoring (TDM) of its metabolites, particularly 6-thioguanine nucleotides (6-TGN), may help to optimize dosing and prevent toxicity. A case series of four Indian patients who developed azathioprine-related myelosuppression is presented. Each patient either expressed a low to intermediate TPMT enzyme activity or a NUDT15 c.415C>T (p.R139C) polymorphism. In all cases, 6-TGN concentrations were measured to assess thiopurine exposure. TPMT phenotyping, NUDT15 genotyping, and 6-TGN monitoring represents an integrated approach to optimize thiopurine therapy.</p>","PeriodicalId":94167,"journal":{"name":"Personalized medicine","volume":" ","pages":"69-73"},"PeriodicalIF":0.0000,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Personalized medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/17410541.2026.2657977","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/4/13 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Thiopurines, a widely used immunosuppressant for autoimmune and inflammatory condition, is associated with potentially severe adverse effects, particularly myelosuppression. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) can largely predict the risk of thiopurine-induced toxicity. Therapeutic drug monitoring (TDM) of its metabolites, particularly 6-thioguanine nucleotides (6-TGN), may help to optimize dosing and prevent toxicity. A case series of four Indian patients who developed azathioprine-related myelosuppression is presented. Each patient either expressed a low to intermediate TPMT enzyme activity or a NUDT15 c.415C>T (p.R139C) polymorphism. In all cases, 6-TGN concentrations were measured to assess thiopurine exposure. TPMT phenotyping, NUDT15 genotyping, and 6-TGN monitoring represents an integrated approach to optimize thiopurine therapy.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
