[Bone marrow depression after azathioprine. New discoveries on an old drug].
Azathioprine, a cytostatic and immunosuppressive drug in use for some 30 years, can give rise to life-threatening neutropenia and thrombocytopenia. This may be caused by unexpectedly high concentrations of cytotoxic metabolites due to abnormally slow inactivation of 6-mercaptopurine (6-MP) by thiopurine S-methyltransferase (TPMT) and/or xanthine oxidase. Low TPMT activity may be due to genetic polymorphism or interaction with drugs such as salicylic acid derivatives, while xanthine oxidase may be inhibited by allopurinol. High TPMT activity, on the other hand, may hamper cytostatic treatment. Safer and more effective treatment with azathioprine and its metabolite 6-MP becomes possible with new laboratory methods for pharmacotherapy monitoring.
Löwhagen
G B
GB
Institutionen för dermatologi och venereologi, Sahlgrenska Universitetssjukhuset, Göteborg.
Lindstedt
G
G
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000378:metabolism; D001379:Azathioprine / Q000009:adverse effects* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects*; D005260:Female; D005838:Genotype; D006402:Hematologic Diseases / Q000139:chemically induced*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000378:metabolism; D015122:Mercaptopurine / Q000009:adverse effects / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009503:Neutropenia / Q000139:chemically induced; D010198:Pancytopenia / Q000139:chemically induced; D012307:Risk Factors
D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; D001379:Azathioprine