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Metabolism of hexamethylmelamine-ring-14C in rats and man.

1974; National Institutes of Health; Volume: 34; Issue: 10 Linguagem: Inglês

John F. Worzalla, Bernard D. Kaiman, Bruce M. Johnson, Guillermo Ramírez, George T. Bryan,

Melamine detection and toxicity

The metabolism of hexamethylmelamine (HMM), an antineoplastic drug, was studied in man and rats. After administration of HMM-ring-14C to two patients, peak plasma levels of radioactivity were seen 1 hr after drug administration and the plasma half-life of radioactivity was 13 hr. Patients excreted 61% of the radioactivity in the urine within 24 hr and 89% within 72 hr. No expired 14CO2 was found in the breath of patients within 6 hr of administration, and less than 0.2% of radioactivity was found in the feces in 48 hr. Rats that were given HMM-ring-14C i.p. excreted 74% radioactivity in urine, 19% in feces, and none as 14CO2 within 24 hr. Urinary metabolites were isolated by ion exchange methods, identified by gas chromatography-mass spectrometry, and quantitated using thin-layer chromatography with a radiochromatogram scanner. The urinary metabolites of HMM in both rats and man were N -demethylated homologs of HMM. These experiments suggest that in man and rats there is no significant metabolic cleavage of the s -triazine ring and that methylmelamines and melamine appear to be the only major urinary metabolites of HMM. In vitro assays for inhibition of dihydrofolate reductase from rat liver revealed that neither HMM nor its metabolites exhibited inhibition of this enzyme.