Work

Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing

Year: 2011

Type: article

Abstract: Thiopurine methyltransferase (TPMT) activity exhibits monogenic co-dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, homozygous TPMT-deficient patients (~1 in 178 to 1 in 3,736 individuals with two nonfunctional TPMT alleles) experience severe myelosuppression, 30-60% of individuals who are heterozygotes (~3-14% of the population) show moderate toxicity, and homozygous wild-type individuals (~86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.

Source: Clinical Pharmacology & Therapeutics

DOI: 10.1038/clpt.2010.320

Authors: M V Relling, E E Gardner, W J Sandborn, K Schmiegelow, C-H Pui, S W Yee, C M Stein, M Carrillo, W E Evans, T E Klein

Institutions: St. Jude Children's Research Hospital, University of California San Diego, University of Copenhagen, Rigshospitalet, University of California, San Francisco, Vanderbilt University, Vanderbilt University Medical Center, Stanford Medicine, Stanford University

Language: English

Topic: Pharmacogenetics and Drug Metabolism

Subfield: Pharmacology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: American Lebanese Syrian Associated Charities, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences

Awards: Pharmacogenomics of Arrhythmia Therapy, PAAR4Kids-Pharmacogenomics of Anticancer Agents Research in Children, The PharmGKB: Catalyzing Research in Pharmacogenetics, PharmGKB: pharmacogenomics knowledge for precision medicine, Pharmacogenomics of Membrane Transporters, Pharmacogenomics of Arrhythmia Therapy, PEDIATRIC ONCOLOGY EDUCATION (YEARS 38 - 42), Cancer Center Support Grant (CCSG)

OpenAlex ID: W2402900764

FWCI: 43.09

Cites: 54

Cited by: 586

Related to: 10