Abstract
The cytotoxic effects of 6-mercaptopurine (6MP) therapy in children show wide variation. A major factor that influences the formation of 6-thioguanine nucleotides (6TGN), which are cytotoxic metabolites of 6M13, is S-methylation which catalyzes 6MP to 6-methylmercaptopurine nucleotides (6MMPN). A total of 33 blood samples were obtained from 6 children, who continuously received 6MP orally for 5-231 (median 72) days. The non-methylated metabolite, 6TGN, and the methylated metabolite, 6MMPN, were measured simultaneously in red blood cells. The ratio of 6MMPN to 6TGN was considered to be related to the degree of S-methylation. The concentrations of 6TGN and 6MMPN varied widely. No subject showed a low concentration of these metabolites that would reflect poor compliance. Wide differences in the ratio of 6MMPN to 6TGN were found among individuals, range from 1.7 to 43.4. However, the ratio was constant in individual children. The simultaneous measurement of 6TGN and 6MMPN concentrations in red blood cells may help to identify pediatric patients who are receiving a suboptimal dose of 6MP.
