Concluding Remarks

The high-performance liquid chromatography measurement of erythrocyte 6-MP metabolites has now become a useful clinical tool for documenting patients' compliance to therapy as well as the adequacy of dosing. Ongoing studies have developed the notion of a therapeutic window of efficacy and toxicity based on the measure of erythrocyte 6-TG and 6-MMP levels. Moreover, prior knowledge of a patient's erythrocyte TPMT enzyme activity may allow physicians to tailor the dosage of either AZA or 6-MP to suite a patient's individual drug metabolism. Those with very low (< 5 U/mL) TPMT activity can be effectively treated (90% response) with 1 mg/kg/d while monitoring complete blood counts and erythrocyte 6-TG levels. Whereas patients with TPMT activity between 5 to 12 U/mL blood show a 70% response rate to a moderate dosing strategy, such as 1.5 mg/kg/d. In patients with above average (> 12 U/mL) TPMT activity, AZA may need to be started at 2.0 mg/kg/d in order to achieve a 40% clinical response. However, higher dosages, such as 2.5 mg/kg/d, are expected to be needed for those with very high (> 20 U/mL) TPMT enzyme activity. In these patients, the careful monitoring of 6-TG and 6-MMP levels may help to guide therapy and identify those patients that preferentially shunt AZA metabolites away from the production of 6-TG, (Cuffari et al, 2004).

Constipation Prescription

Constipation Prescription

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