Hexamethylmelamine and pentamethylmelamine tissue distribution in M5076/73A ovarian cancer-bearing mice

The distribution of hexamethylmelamine (HMM), pentamethylmelamine (PMM), and their metabolites N₂,N₂,N₄,N₆-tetramethylmelamine (TMM) and N₂,N₄,N₆-trimethylmelamine (TriMM) was investigated in different tissues of M5076/73A ovarian cancer-bearing mice given 100 mg/kg ip of either drug. The area-under-the-curve (AUC) values of HMM and PMM, expressed in μg/g x min after these drug treatments, were 2432 and 1296 in tumor, 6290 and 8141 in liver, 9779 and 21,294 in spleen, 6840 and 10,800 in kidney, 4003 and 4295 in heart, 1569 and 1327 in brain, 163,689 and 50,809 in adipose tissue, 88,725 and 45,070 in lymph nodes, 15,033 and 18,992 in small intestine, and 393 and 351 in plasma, respectively. The elimination rate of HMM for the different organs was similar, with a half-life of 37-48 mins; PMM disappeared with more variability, the half-life being 19-46 mins. While TMM concentrations were not very different from those of HMM or PMM, TriMM was much higher in all organs evaluated, particularly the brain, where AUC values were 21-24 times those of the administered drug.