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Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing.
- Source :
-
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2011 Mar; Vol. 89 (3), pp. 387-91. Date of Electronic Publication: 2011 Jan 26. - Publication Year :
- 2011
-
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.
- Subjects :
- Antimetabolites, Antineoplastic administration & dosage
Antimetabolites, Antineoplastic adverse effects
Antimetabolites, Antineoplastic metabolism
Azathioprine adverse effects
Azathioprine metabolism
Dose-Response Relationship, Drug
Genotype
Humans
Immunosuppressive Agents administration & dosage
Immunosuppressive Agents adverse effects
Immunosuppressive Agents metabolism
Mercaptopurine adverse effects
Mercaptopurine metabolism
Methyltransferases metabolism
Thioguanine adverse effects
Thioguanine metabolism
Azathioprine administration & dosage
Mercaptopurine administration & dosage
Methyltransferases genetics
Thioguanine administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1532-6535
- Volume :
- 89
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 21270794
- Full Text :
- https://doi.org/10.1038/clpt.2010.320