AI Article Synopsis
- Thiopurine S-methyltransferase (TPMT) is crucial for metabolizing thiopurine drugs, and its decreased activity can lead to serious side effects.
- A high-performance liquid chromatographic (HPLC) assay was developed to measure the conversion of 6-mercaptopurine into 6-methylmercaptopurine in red blood cells.
- The study found varying TPMT activity levels among healthy individuals, with some showing significantly lower activity linked to specific genetic variants, supporting the need for personalized dosing of thiopurine medications.
Article Abstract
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.
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| http://dx.doi.org/10.1016/s0009-8981(02)00184-5 | DOI Listing |
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