[Genetic polymorphism and treatment of chronic bowel inflammatory diseases: the example of azathioprine].
Azathioprine is an immunosuppressive drug used in the treatment of inflammatory bowel disease. It is a prodrug that is hydrolysed to 6-mercaptopurine, which represents the active form. Azathioprine is also used in the treatment of leukaemia in children and in organ transplantation. Azathioprine treatment is associated with adverse effects such as leukopenia and aplasia. These adverse effects are related to a single nucleotide polymorphism, including the inability of cells to synthesize thiopurine methyltransferase (TPMT). TPMT is a detoxification enzyme that limits 6-thioguanine nucleotide production and thereby interferes with normal DNA and RNA synthesis. This review presents the different approaches used for azathioprine therapeutic monitoring in IBD treatment and discusses the discrepancies in recent clinical trials.
Bessard
Germain
G
Laboratoire de pharmacologie, Hopital Michallon, CHU Grenoble, Grenoble, France. gbessard@chu-grenoble.fr
Hardy
Gaëlle
G
Chartier
Alain
A
Stanke-Labesque
Françoise
F
D001379:Azathioprine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001711:Biotransformation; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000502:physiology*
D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine