STUDIES OF THE PHARMACOLOGY OF N-METHYLFORMAMIDE IN MICE

When 400 mg/kg of 14C-methyl-labeled N-methylformamide (NMF) [an antineoplastic drug] was injected i.p. into mice, the curve for plasma concentration of radioactivity vs. time was superimposable on the curve obtained by measuring unmetabolized NMF with gas-liquid chromatography during the 1st 24 h. Radioactivity in plasma was measureable for 8 days after NMF administration, but NMF was not measurable by gas chromatography beyond 24 h after administration. Radioactivity was eliminated from the plasma after 60 h, with an apparent half-life of 71.1 h. Of the radioactivity injected with NMF, 73.6% was recovered in the urine in 24 h; 26.4% of this was unchanged NMF. Three percent of the administered radioactivity was exhaled as 14CO2 in 7 h at a constant rate of 0.007% per min. One urinary metabolite was a stable precursor of formaldehyde, which decomposed to formaldehyde only after alkaline hydrolysis and may well be N-(hydroxymethyl)-formamide. The areas under the plasma concentration vs. time curve were estimated after i.p., i.v. and oral administration of NMF. The bioavailability of NMF was 1.01 after oral administration and 1.10 after i.p. administration.