LACTOSE CONJUGATION OF SULFONAMIDE DRUGS IN THE LACTATING DAIRY-COW

1. C-14-Sulphamethazine (4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene-[(U-C)-C-14]-sulphonamide; 220 mg/kg of body weight) was given orally or i.v. to lactating dairy cows. Milk collected from 0-48 h after dosing accounted for 2.0% (oral dose) and 1.1% (i.v. dose) of the total C-14-activity administered. 2. Sulphamethazine accounted for 70-79% (oral dose) and 54-75% (i.v. dose) of the total C-14 in milk samples collected from 0-48 h after dosing. N4-acetylsulphamethazine accounted for 12% (oral dose) and 1-4% (i.v. dose) of the C-14 in milk. 3. The major C-14-labelled metabolite in the milk was isolated and identified as the N4-lactose conjugate of sulphamethazine, a unique type of metabolite not previously reported. This metabolite accounted for 10-14% (oral dose) and 9-20% (i.v. dose) of the C-14-activity in the milk collected from 0-48 h after dosing with C-14-sulphamethazine. 4. N4-lactose conjugates of sulphapyridine, sulphamerazine, sulphathiazole, sulphadimethoxine and sulphaquinoxaline were present in the milk from cows orally dosed with these five sulphonamide drugs.