Azathioprine toxicity, 6-mercaptopurine accumulation and the “poor” 6-thiopurine methylator phenotype
✍ Scribed by A. Escousse; C. Sgro; G. Rifle; C. Mousson; G. Zanetta; D. Chevet
- Publisher
- Springer
- Year
- 1995
- Tongue
- English
- Weight
- 152 KB
- Volume
- 48-48
- Category
- Article
- ISSN
- 0031-6970
No coin nor oath required. For personal study only.
✦ Synopsis
The therapeutic use of the immunosuppressive drug Azathioprine (AZA) in preventing rejection in allograft transplant recipients is limited by its haematological toxicity, mainly leukopenia.
AZA is a "prodrug", spontaneously converted in the body to two derivatives, 6 mercaptopurine (6MP), and a nitroimidazole derivative. The production and accumulation of 6-thiomercaptopurine (6MP) and 6-thioguanine (6TG), another AZA metabolite, could be of importance in causing the myelotoxic effect as accumulation of the 6-thiopurine derivatives appears to be the most important factor in producing toxicity. The dose dependent haematological toxicity of AZA appears to be linked to the "poor" 6-thiopurine methyl transferase (TPMT) activity phenotype described by Weinshilboum [1].
Thus 6-TPMT activity determination in erythrocytes of transplanted patients could be a good "in vitro" predictive measure of the haematological risk of AZA immunosuppressive treatment. However, the exact significance of the accumulation of 6-thiopurine derivatives in AZA-treated subjects is poorly understood, and the relationship between accumulation of these active metabolites and the "poor" methylator phenotype remains unknown.