Pharmacogenetics of Thiopurine S-Methyltransferase and Thiopurine Therapy

@article{Evans2004PharmacogeneticsOT,
  title={Pharmacogenetics of Thiopurine S-Methyltransferase and Thiopurine Therapy},
  author={W. Evans},
  journal={Therapeutic Drug Monitoring},
  year={2004},
  volume={26},
  pages={186-191}
}
  • W. Evans
  • Published 2004
  • Biology, Medicine
  • Therapeutic Drug Monitoring
Abstract: Most medications exhibit wide interpatient variability in their efficacy and toxicity. For many medications, these interindividual differences result in part from polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and/or drug targets (eg, receptors, enzymes). Pharmacogenomics is a burgeoning field aimed at elucidating the genetic basis of differences in drug efficacy and toxicity, using genome-wide approaches to identify the network of genes that govern an… Expand
Clinical pharmacology and pharmacogenetics of thiopurines
TLDR
The recent advances in the knowledge of the mechanism of action as well as the molecular basis and interethnic variations of TPMT and inosine triphosphate pyrophosphatase are reviewed and an update on pharmacokinetics, metabolism, drug-drug interactions, safety, and tolerability of thiopurine drugs is provided. Expand
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Polymorphisms in drug metabolizing enzymes, transporters and/or pharmacological targets of drugs may profoundly influence the dose-response relationship between individuals sometimes exacerbating theExpand
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TLDR
This review highlights the current approaches to improve the clinical impact of 6-MP in childhood ALL in context with polymorphic TPMT gene with various rapid and inexpensive assays. Expand
Individualization of thiopurine therapy: thiopurine S-methyltransferase and beyond.
TLDR
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lnterpatient variabiff1y among medication doses has been a longstanding obstacle tor many prescribers. Some medications result in increased morbidity and mortalffy in a small percentage of theExpand
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Evaluation of different regimens and tumor types showed that polymorphisms can have different, sometimes even contradictory, pharmacokinetic and pharmacodynamic effects in different tumors in response to different drugs. Expand
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TLDR
The future of pharmacogenetics will be in treatment models in which patient characteristics are combined with data on polymorphisms in multiple genes, and these models should focus on pharmacodynamic parameters, variations in the expression of drug transporter proteins, and predictors of toxicity. Expand
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The recessive deficiency in thiopurine methyltransferase (TPMT), caused by germ-line polymorphisms in TPMT, can cause severe toxicity after mercaptopurine. However, the significance of heterozygosityExpand
Pharmacogenetics in inflammatory bowel disease.
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The variants in genes that influence either the efficacy or toxicity of common drugs used in the treatment of inflammatory bowel diseases (IBD), ulcerative colitis (UC), and Crohn's disease (CD) are described. Expand
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TLDR
Clinicians should be aware that TPMT SNPs do not explain all leucopenic events and that T PMT measurements cannot replace the need for continued monitoring of leucocyte counts in AZA/6-MP treated patients. Expand
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