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Clin Chim Acta. 2002 Sep;323(1-2):147-50.

Thiopurine S-methyltransferase activity in Japanese subjects: metabolic activity of 6-mercaptopurine 6-methylation in different TPMT genotypes.

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  • 1Department of Pharmacy, Faculty of Medicine, University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan.



Thiopurine S-methyltransferase (TPMT), which exhibits autosomal codominant polymorphism, plays an important role in the metabolism of thiopurine drugs such as mercaptopurine, thioguanine and azathioprine. Decreased activity of TPMT is associated with severe hematopoietic toxicity after administration of standard doses of these drugs.


We developed a specific high-performance liquid chromatographic (HPLC) assay for measuring 6-methylmercaptopurine (6-MMP) formed from 6-mercaptopurine (6-MP) in red blood cells (RBC) lysates. The assay was used to study the distribution of TPMT activities in 44 healthy Japanese subjects with different TPMT genotypes.


The TPMT activities in the subjects ranged from 17.9 to 37.1 pmol/h/mgHb. The TPMT activity of one subject with TPMT*1/*3C (17.9 pmol/h/mgHb) was 40% lower than the mean value of TPMT activities in 43 subjects with TPMT*1/*1 (29.6+/-4.3 pmol/h/mgHb).


This sensitive and reproducible HPLC assay for determination of TPMT activity in RBC clinical studies has been designed to optimize dosage regimens of thiopurine drugs.

[PubMed - indexed for MEDLINE]
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