The disposition of ¹⁴C-levamisole in the lactating cow

Abstract

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 0·6 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 % (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.