Pharmacokinetics of hexamethylmelamine and pentamethylmelamine in mice

Plasma pharmacokinetics of hexamethylmelamine (HMM) and pentamethylmelamine (PMM) were investigated after ip administration of doses of 50 or 100 mg/kg to M5076/73A ovarian tumor-bearing C57BL/6J female mice. The half-life of HMM was 44.5-49 mins; the half-life of PMM was 7.6-8.7 mins. The area under the concentration-versus-time curve (AUC) was also much higher for HMM than for PMM. The AUC for the metabolite N2,N2,N4,N6-tetramethylmelamine (TMM) was seven to ten times higher than that of the parent compounds. After incubation with mouse liver microsomes and cofactors, the rates of metabolism of HMM and PMM were essentially the same. Plasma protein binding was 94%, 71%, and 50% for HMM, PMM, and TMM, respectively.