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Related Experiment Video

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Published on: November 23, 2019

Implementation of TPMT testing.

Lynne Lennard¹

¹Clinical Pharmacology Unit, Department of Human Metabolism, University of Sheffield, Sheffield, UK.

British Journal of Clinical Pharmacology

|August 22, 2013

Summary

Thiopurine methyltransferase (TPMT) enzyme activity influences thiopurine drug efficacy and toxicity. TPMT testing before treatment identifies individuals at risk of severe side effects, ensuring safer drug use.

Keywords:

TPMT azathioprine childhood leukaemia mercaptopurine thioguanine nucleotides thiopurine methyltransferase

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TMT Sample Preparation for Proteomics Facility Submission and Subsequent Data Analysis

TMT Sample Preparation for Proteomics Facility Submission and Subsequent Data Analysis

Published on: June 8, 2020

Area of Science:

Pharmacogenetics
Clinical enzymology

Background:

Thiopurine drugs (azathioprine, mercaptopurine, thioguanine) are substrates for thiopurine methyltransferase (TPMT).
Genetic polymorphism in TPMT affects enzyme activity, with 1 in 300 lacking activity and 11% having intermediate activity.
TPMT deficiency is linked to severe myelosuppression and idiosyncratic drug reactions.

Purpose of the Study:

To review factors influencing TPMT enzyme activity and its measurement.
To highlight the importance of accurate TPMT status classification for thiopurine therapy.
To discuss the clinical adoption and cost-effectiveness of TPMT testing.

Main Methods:

Review of factors affecting TPMT enzyme activity.
Discussion of TPMT genotype-phenotype concordance.
Analysis of clinical recommendations and cost-effectiveness.

Main Results:

TPMT deficiency confers a high risk of severe bone marrow toxicity with standard thiopurine doses.
Heterozygotes face an increased risk of myelosuppression.
Concordance between TPMT genotype and phenotype is not always 100%, especially for intermediate activities.

Conclusions:

TPMT testing is crucial for identifying individuals at risk before initiating thiopurine therapy.
Testing is cost-effective and widely available, with varying adoption across specialties.
Mandatory testing is recommended, particularly for childhood leukemia treatment with mercaptopurine.