Abstract
Azathioprine (AZA) has been given to transplanted patients since 1963 (1), but despite extensive use its metabolism is still not completely understood. After oral administration, it is converted rapidly to 6-mercaptopurine (6MP), mainly in the liver and the gut (2). 6MP is metabolised by three competing pathways (Figure 1): A) conversion to 6-thioinosinic acid by hypoxanthine guanine phosphoribosyltransferase (HPRT) and thence thioguanine nucleotides which exert their cytotoxicity by incorporation into DNA and RNA (2,3); B) catabolism by xanthine oxidase (XOD) to 6-thiouric acid; C) conversion to 6-methyl mercaptopurine (6MeMP) by the enzyme thiopurine methyl transferase (TPMT), which has a wide range of activity in the normal population and is inherited in a autosomal codominant fashion (3,4).
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Chocair, P.R., Duley, J.A., Simmonds, H.A., Cameron, J.S. (1991). Thiopurine Methyltransferase Activity and Efficacy of Azathioprine Immunosuppression in Transplant Recipients. In: Harkness, R.A., Elion, G.B., Zöllner, N. (eds) Purine and Pyrimidine Metabolism in Man VII. Advances in Experimental Medicine and Biology, vol 309A. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-2638-8_13
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