Disposition of methyl ethyl ketoxime in the rat after oral, intravenous and dermal administration.
1. The disposition of 14C-methyl ethyl ketoxime (MEKO) was determined in the male F344 rat following oral, intravenous (i.v.) and dermal administration. 2. Oral doses of 2.7, 27 and 270 mg/kg were primarily excreted as CO2 (71-49%) in decreasing percentage as the dose increased. Excretion in urine (13-26%) and as volatiles (5-18%) increased as the dose increased. Five to 6% of the dose remained in the major tissues after 72 h. 3. An i.v. dose of 2.7 mg/kg was also principally excreted as CO2 (48.8%) with excretion in urine and as expired volatiles accounting for 21.4 and 11.4%, respectively. About 7% of the administered radioactivity remained in the tissues after 72 h. 4. Following dermal administration, 13 and 26% of a 2.7 and 270 mg/kg dose, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption. 5. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles.
Burka
L T
LT
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Black
S R
SR
Mathews
J M
JM
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002074:Butanones / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D007275:Injections, Intravenous; D008297:Male; D010091:Oximes / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002074:Butanones; D010091:Oximes; C104767:2-butanone oxime