Format

Send to

Choose Destination
Oncology. 2014;86(3):152-8. doi: 10.1159/000357407. Epub 2014 Mar 12.

Augmenting clinical interpretability of thiopurine methyltransferase laboratory evaluation.

Author information

1
Department of Pharmacology, Masaryk University School of Medicine, Brno, Czech Republic.

Abstract

OBJECTIVE:

Individuals with decreased thiopurine methyltransferase (TPMT) activity are at risk of adverse effects of thiopurine administration whereas its increased activity may inactivate drugs faster. We evaluated genotype-phenotype correlations in patients with suspected hematological malignancies and inflammatory bowel disease from our region based on findings of nonlinear TPMT enzyme kinetics previously unreported.

PATIENTS AND METHODS:

The study group comprised 267 individuals. They were screened for the most common variants of low TPMT activity. TPMT activity was measured in erythrocytes using the HPLC rate-blanked method.

RESULTS:

Thirty-three patients (12.4%) were heterozygous (26 were TPMT*1/*3A, 5 TPMT*1/*2, 2 TPMT *1/*3C) and 1 was a compound heterozygote (*2/*3A). Normal and low normal TPMT activities substantially overlapped in wild-type and heterozygous individuals, whereas high activities were found in 29 wild-type genotyped patients. Extreme and life-threatening toxicity was observed in the compound heterozygote patient.

CONCLUSION:

Activity measurement performed at diagnosis provides clinicians with information on immediate pharmacokinetic-related adverse events and/or hypermetabolism, and genotyping may indicate the rate of pharmacodynamic thioguanine nucleotide accumulation due to slower overall thiopurine metabolism.

PMID:
24643197
DOI:
10.1159/000357407
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland
Loading ...
Support Center