Document Detail


Thiopurine S-methyltransferase activity in Japanese subjects: metabolic activity of 6-mercaptopurine 6-methylation in different TPMT genotypes.
MedLine Citation:
PMID:  12135816     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors:
Akihito Nishida; Takahiro Kubota; Yasuhiko Yamada; Katsumi Higashi; Kiyoshi Kitamura; Kazuhiko Nakahara; Tatsuji Iga
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinica chimica acta; international journal of clinical chemistry     Volume:  323     ISSN:  0009-8981     ISO Abbreviation:  Clin. Chim. Acta     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-07-23     Completed Date:  2002-10-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1302422     Medline TA:  Clin Chim Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  147-50     Citation Subset:  IM    
Affiliation:
Department of Pharmacy, Faculty of Medicine, University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
6-Mercaptopurine / chemistry,  metabolism*
Asian Continental Ancestry Group / genetics*
Chromatography, High Pressure Liquid
Genotype
Humans
Methylation
Methyltransferases / genetics*,  metabolism*
Molecular Structure
Sensitivity and Specificity
Chemical
Reg. No./Substance:
50-44-2/6-Mercaptopurine; EC 2.1.1.-/Methyltransferases; EC 2.1.1.67/thiopurine methyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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