THE DISPOSITION OF C-14 LEVAMISOLE IN THE LACTATING COW

1. C-14-Levamisole etrahydro-6-phenyl[U-C-14]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 fro m 0.48 h after dosing and tissues mere collected 48 h after dosing. 2. C-14-Labelled residues (ppm C-14-levamisole equivalents) in blood wer e highest at 3 h (2 2 ppm, oral dose) or 6 h (2 1 ppm, subcutaneous do se) and then declined to less than 05 ppm 48 h after dosing. 3. C-14-L abelled 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 or al and subcutaneously dosed animals, respectively) and declined to 0.0 6 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% (subcutan eous dose) of the total C-14-activity administered as C-14-levamisole. The parent compound, C-14-levamisole, accounted for 12% or less (decl ined with time after dosing) of the total C-14-activity in the milk. T hree C-14-labelled metabolites (formed by oxidation of imidazoline rin g and/or opening of thiazolidine ring) in the milk were isolated and i dentified. 4. Urinary excretion accounted for 83% and 84% and faecal e xcretion accounted for 11% and 9% of the total C-14-activity given ora lly and subcutaneously, respectively, as C-14-levamisole. No C-14-leva misole was detected in the urine; the major urinary metabolite (formed by opening of thiazolidine ring) was isolated and identified. 5. The C-14-activity remaining in the animals 48 h after dosing was widely di stributed in body tissues; however, the concentration in the liver was substantially higher than in all other tissues examined. Less than 5% of the C-14-activity in the liver was present as C-14-levamisole.