Pharmacogenomics of azathioprine and 6-mercaptopurine in gastroenterologic therapy

The elimination of azathioprine and 6-mercaptopurine is greatly influenced by polymorphisms in the enzymes responsible for their metabolism. Patients who are deficient in thiopurine methyltransferase (TPMT) are at an increased risk for azathioprine- and 6-mercaptopurine-induced toxicities because of the accumulation of toxic metabolites, and patients with high TPMT activity may not receive maximum benefit because of the increased clearance. Therefore, routine TPMT genotyping prior to the initiation of azathioprine or 6-mercaptopurine therapy should be considered to decrease the risk of severe and possibly preventable adverse effects and to identify patients who might benefit from higher doses. However, measuring the TPMT activity at baseline is not a substitute for monitoring white blood cell counts throughout therapy because drug therapy and/or other conditions may still cause myelosuppression in these patients.