The disposition of 14C-levamisole in the lactating cow.
1. 14C-Levamisole 1(-)-2,3,5,6-tetrahydro-6-phenyl[U-14C]imidazo[2,1-b]-thiazole was administered orally and subcutaneously to lactating cows (8 mg/kg body weight). Urine, faeces, milk and blood samples were collected from 0-48 h after dosing and tissues were collected 48 h after dosing. 2. 14C-Labelled residues (ppm 14C-levamisole equivalents) in blood were highest at 3 h (2.2 ppm, oral dose) or 6 h (2.1 ppm, subcutaneous dose) and then declined to less than 0.5 ppm 48 h after dosing. 3. 14C-Labelled residues in milk were highest in samples collected from 0-12 h after dosing (1.55 ppm and 1.86 ppm of levamisole equivalents from oral and subcutaneously dosed animals, respectively) and declined to 0.06 ppm in milk collected from 36-48 h after dosing. Milk collected from 0-48 h after dosing accounted for 0.2% (oral dose) and 0.6% (subcutaneous dose) of the total 14C-activity administered as 14C-levamisole. The parent compound, 14C-levamisole, accounted for 12% or less (declined with time after dosing) of the total 14C-activity in the milk. Three 14C-labelled metabolites (formed by oxidation of imidazoline ring and/or opening of thiazolidine ring) in the milk were isolated and identified. 4. Urinary excretion accounted for 83% and 84% and faecal excretion accounted for 11% and 9% of the total 14C-activity given orally and subcutaneously, respectively, as 14C-levamisole. No 14C-levamisole was detected in the urine; the major urinary metabolite (formed by opening of thiazolidine ring) was isolated and identified. 5. The 14C-activity remaining in the animals 48 h after dosing was widely distributed in body tissues; however, the concentration in the liver was substantially higher than in all other tissues examined. Less than 5% of the 14C-activity in the liver was present as 14C-levamisole.
Paulson
G D
GD
US Department of Agriculture, Agricultural Research Service, Biosciences Research Laboratory, Fargo, ND 58105, USA.
Feil
V J
VJ
D000284:Administration, Oral; D000818:Animals; D000969:Antinematodal Agents / Q000378:metabolism / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D002417:Cattle; D005243:Feces / Q000737:chemistry; D005260:Female; D007267:Injections; D007774:Lactation; D007978:Levamisole / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008892:Milk / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013997:Time Factors; D014018:Tissue Distribution
D000969:Antinematodal Agents; D002250:Carbon Radioisotopes; D007978:Levamisole