title: Disposition and metabolism of N,N-dimethylacetoacetamide in male F344 and Wistar-Han rats and female B6C3F1 mice.
abstract: N,N-dimethylacetoacetamide (DMAAm) is a β-dicarbonyl compound used as an industrial intermediate. This study investigated the disposition and metabolism of [¹⁴C]DMAAm in male rats and female mice. A single oral dose of [¹⁴C]DMAAm (target dose of 10 or 130 mg/kg) was administered to male F344 and Wistar-Han rats. [¹⁴C]DMAAm was almost completely absorbed and excreted in urine, with ca. 80-90% of the dose recovered within 24 h for both rat strains. Fecal excretion and CO₂ exhalation were minimal (1 and 2%, respectively). Less than 3% of the dose remained in tissues at 24 h. There was no apparent dose- or strain-related difference in the disposition of [¹⁴C]DMAAm in rats. In female B6C3F1 mice administered 8 mg/kg [¹⁴C]DMAAm, 80% of the administered radioactivity was recovered in urine and cage rinse in 24 h. Urinary metabolites were isolated and characterized by liquid chromatography /mass spectrometry following oral administration of 435 mg/kg [(¹⁴C]DMAAm in male F344 rats. Metabolism occurred via reduction of the 3-keto group and oxidation of the N-methyl groups, to give N,N-dimethyl-3-hydroxybutanamide, N-methyl-N-hydroxymethyl-3-hydroxybutanamide, and N-hydroxymethyl-3-hydroxybutanamide, and N-demethylation to give N-monomethylacetoacetamide (MMAAm).
authors.affiliation: RTI International , Research Triangle Park, NC 27709-2194, USA. Fennell@rti.org
authors.forename: Timothy
authors.initials: T
authors.lastname: Fennell
authors.forename: Scott
authors.initials: S
authors.lastname: Watson
authors.forename: Rodney
authors.initials: R
authors.lastname: Snyder
authors.forename: Robert
authors.initials: R
authors.lastname: Jeffcoat
authors.forename: Suramya
authors.initials: S
authors.lastname: Waidyanatha
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D000818:Animals; D002853:Chromatography, Liquid; D005260:Female; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008815:Mice, Inbred Strains; D009928:Organ Specificity; D011851:Radioactivity; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D000577:Amides; C569817:N,N-dimethylacetoacetamide