lntracellular thiopurine nucleotides and azathioprine myelotoxicity in organ transplant patients

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Abstract
Despite widespread use of azathioprine in organ transplant recipients, the mechanism of its myelotoxicity remains unclear. The aim of this study was to assess the importance of thiopurine metabolites on bone marrow toxicity. We investigated the relationship between intracellular concentrations of 6-thioguanine (6-TGN), 6-mercaptopurine (6-MPN) and 6-thioxanthine (6 TXN) nucleotides and the absolute count of white or red cells in forty-seven lung or heart/lung transplant patients after oral administration of azathioprine. No significant correlation between red cell concentrations of 6-TGN or total thiopurine metabolites and white or red cell counts was found, with no difference between the sexes. Likewise, high 6-TGN levels were not related to bone marrow depletion. These results suggest that red blood cell 6-TGN alone do not predict the haematopoietic toxicity of azathioprine.