DISPOSITION AND METABOLISM OF PENTAMETHYLMELAMINE AND HEXAMETHYLMELAMINE IN RABBITS AND HUMANS

Abstract

The disposition and metabolism of pentamethylmelamine (PMM) and hexamethylmelamine (HMM) [possible antitumor agents] were studied in the rabbit and the disposition of PMM was studied in humans. Parent compound and metabolites were identified by thin-layer chromatography, gas chromatography and gas chromatography/mass spectrometry analyses. Plasma elimination in both species following i.v. administration of each drug was best described by a 2-compartment open model. Both compounds were extensively demethylated with < 1% of the total dose administered recovered in the urine over 24 h. The areas under the plasma time-concentration curves of PMM and HMM following i.v. administration. Gastrointestinal absorption was rapid and efficient with 75-89% of drug equivalents recoverable in the urine after p.o. administration of [R-14C]PMM or [R-14C]HMM to rabbits. Reduced bioavailability of PMM and HMM p.o. appears to be a consequence of rapid metabolism presumably in the liver.