Plasma levels and urinary excretion of hexamethylmelamine following oral administration to human subjects with cancer

An ultraviolet spectrophotometric analytical method was used to study the plasma levels and urinary metabolites of cancer patients following oral administration of the antineoplastic agent hexamethylmelamine (HMM). Maximum plasma levels varied directly with the dose administered and occurred 2 to 3 hours after drug ingestion. At clinically employed dosage levels no intact HMM was present in the plasma, but two metabolites of this drug were detected. Hemolyzed erythrocytes contained no HMM or drug metabolites. Nearly 19 per cent of a single oral dose of HMM was excreted in the urine 0 to 24 hours after administration, with an additional 12 per cent appearing between 24 and 48 hours. Following prolonged continual daily administration of HMM, 50 to 65 per cent of a daily dose was recovered from the urine as drug metabolites. At least 3 maior urinary metabolites of HMM were found in urine, but no unmetabolized HMM was recovered. These data suggest that the metabolism of HMM may be significantly different from that of its structural analogue triethylenemelamine.