Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update.

• 影响指数: 6.903
• 发表时间: 05 2019
• 来源期刊: Clin Pharmacol Ther
• DOI: 10.1002/cpt.1304
• PMID: 30447069
• 文章类型: Journal Article
• 中科院分区: Q1
• 方向: 医学
• 作者列表: Relling MV,Schwab M,Whirl-Carrillo M,Suarez-Kurtz G,Pui CH,Stein CM,Moyer AM,Evans WE,Klein TE,Antillon-Klussmann FG,Caudle KE,Kato M,Yeoh AEJ,Schmiegelow K,Yang JJ

Mesh: Antimetabolites, Antineoplastic / administration & dosage pharmacokinetics; Azathioprine / administration & dosage pharmacokinetics; Dose-Response Relationship, Drug; Drug Dosage Calculations; Humans; Inactivation, Metabolic / genetics; Mercaptopurine / administration & dosage pharmacokinetics; Methyltransferases / genetics; Pharmacogenetics; Pharmacogenomic Testing; Pyrophosphatases / genetics; Thioguanine / administration & dosage pharmacokinetics

Abstract

Thiopurine methyltransferase (TPMT) activity exhibits a monogenic codominant inheritance and catabolizes thiopurines. TPMT variant alleles are associated with low enzyme activity and pronounced pharmacologic effects of thiopurines. Loss-of-function alleles in the NUDT15 gene are common in Asians and Hispanics and reduce the degradation of active thiopurine nucleotide metabolites, also predisposing to myelosuppression. We provide recommendations for adjusting starting doses of azathioprine, mercaptopurine, and thioguanine based on TPMT and NUDT15 genotypes (updates on www.cpicpgx.org).