Pharmacokinetics and metabolism of ethylenediamine in the swiss webster mouse following oral or intravenous dosing.
Male Swiss Webster mice were given an intravenous dose of 50 mg/kg, or an oral gavage dose of 5, 50 or 500 mg/kg [1, 2-(14)C]-ethylenediamine dihydrochloride, and its fate was followed for 48 h. Ethylenediamine (EDA) was readily absorbed from the gut (bioavailability, 87% measured at 50 mg/kg). Absorption was rapid as the EDA concentration in plasma reached a maximum at about 1 h after dosing. 14C-EDA-derived radioactivity was distributed throughout the body, with the liver and kidney attaining the highest concentration among the major organs. Urine was the major route of excretion, accounting for over half of the dose. About 4-13 and 8% of the dose was eliminated in the feces and as expired CO(2), respectively. Excretion was quite rapid, with over 70% of the applied dose eliminated within 24 h. The principal metabolite in the urine was N-acetylethylenediamine. There was some indication that the metabolism of EDA in the mouse might be saturated at 500 mg/kg, as the percentage of N-acetylethylenediamine excreted in the urine decreased markedly, with a concomitant shift to a higher proportion of unchanged EDA, when compared with the lower dosages.
Leung
H W
HW
Union Carbide Corporation, 39 Old Ridgebury Road, Danbury, CT 06817-0001, USA. leunghw@ucarb.com
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D005029:Ethylenediamines; C031234:ethylenediamine