Thiopurine methyltransferase enzyme activity determination (Part 3)
The lower the inherited TPMT activity, the more 6-MP is available for conversion to toxic thiopurine nucleotide metabolites and the higher the myelotoxicity. In TPMT-deficient patients, high concentrations of 6-TG nucleotides accumulate in hematopoietic tissue, thereby contributing to toxicity. In the case of IBD, increased 6-TG levels may correlate positively with increased clinical responses and leukopenia . The accumulation of the end products of TPMT activity, including 6-MMP nucleotide metabolites, has been implicated as a cause of hepatotoxicity. Clinically, TPMT activity can be measured using the red blood cell TPMT assay, which reveals TPMT activity in leukocytes, and in liver and kidney cells. Various mutant alleles have been identified using polymerase chain reaction techniques, and one study has shown a 98% concordance between TPMT genotype and TPMT phenotype as determined by the red blood cell assay.
In the management of IBD through AZA treatment, patients are normally started on a low dose of AZA combined with frequent monitoring of blood cell counts, and AZA doses are titrated to therapeutic levels over many months. The extended titration process is primarily used to identify adverse events. Given the positive correlation between phenotypes and TPMT activity, it seems possible that if the TPMT activity were known at the start, AZA might be prescribed at higher initial doses for certain patients, and less frequent blood count monitoring in the case of these high-expression patients might decrease direct health care costs. You can shop for the medicine you need for treating the condition mentioned above right here at the my canadian pharmacy. This pharmacy offers a large selection of medications available over the internet at amazingly low prices.