염증성 장질환에서 Azathioprine과 6-Mercaptopurine 맞춤 처방

Abstract

Immunosuppressors, 6-mercaptopurine (6-MP) and its prodrug azathioprine, are used frequently for the treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn`s disease and primarily for the maintenance of remission. The 6-MP is either inactivated to 6-methylmercaptopurine by thiopurine methyltransferase (TPMT) or to 6-thiouric acid by xanthine oxidase. On the other hand, it can be activated via a multistep enzymatic pathway to the putative active metabolites, 6-thioguanine nucleotides (6-TGN). Clinical responsiveness and side effects are associated with TPMT genotype and phenotype because the enzymatic activity of TPMT is genetically determined. Until now, significant proportion of patients with proper indication are not using immunosuppressors because of safety concern and delayed onset of action. Recently, gastroenterologists who accept immunomodulators as the treatment method for IBD are increasing on the basis of favorable results regarding efficacy and safety. The recent application of pharmacogenetics, the study on variability of drug response due to genetic factors, has provided a chance for tailoring doses in the individual patients.