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The thiopurines azathioprine and 6-mercaptopurine (6-MP) are effective drugs in steroid-dependent and refractory inflammatory bowel disease patients. Therapeutic drug monitoring (TDM) is a new concept to improve drug efficacy and prevent toxic adverse events. As thiopurine metabolism is influenced by genetic polymorphisms of methylating enzymes, metabolite levels may vary considerably, enabling significant adverse effects. In the present paper five patients are described to demonstrate the clinical usefulness of TDM when applying thiopurines for inflammatory bowel disease. Emphasized are patients with liver function test abnormalities and myelosuppression due to inappropriate 6-MP metabolite levels, and subsequently the treatment of these events. In addition, sophisticated 6-MP metabolite level-guided therapy, including non-compliance, is demonstrated. These cases demonstrate that TDM may improve effectivity and safety of thiopurine treatment.