Pharma 6-thioguanine

Similar to 6-MP, the absorption of oral 6-TG is also incomplete and erratic. The peak concentration in the plasma is reached in 2 to 4 hours after ingestion. When 6-TG is administered, it is converted to the S-methylation product, 2-amino-6-methylthiopurine by thiopurine methyltransferase (TPMT), which appears in the urine. Patients with low or intermediate TPMT activity accumulate higher concentrations of thioguanine cytotoxic metabolites compared to patients with normal TPMT activity. This results in unexpectedly high myelosuppression and has also been associated with the occurrence of secondary malignancies. Approximately 3 percent of whites and blacks express either a homozygous deletion or mutation of the TPMT gene. Because an estimated 10 percent of patients may be at increased risk for toxicity because of a heterozygous deletion or mutation of TPMT, TPMT genotyping is recommended before therapy. To a lesser extent, 6-thioxanthine and 6-thiouric acid are also formed by the action of guanase. Because the deamination product 6-thioanthine is an inactive metabolite, 6-TG may be administered along with allopurinol without any dose reduction