Lactose conjugation of sulphonamide drugs in the lactating dairy cow.

1. 14C-Sulphamethazine (4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene-[U-14C]-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 14C-activity administered. 2. Sulphamethazine accounted for 70-79% (oral dose) and 54-75% (i.v. dose) of the total 14C in milk samples collected from 0-48 h after dosing. N4-acetylsulphamethazine accounted for 1-2% (oral dose) and 1-4% (i.v. dose) of the 14C in milk. 3. The major 14C-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 14C-activity in the milk collected from 0-48 h after dosing with 14C-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.

The isolation and identification of 14C-sulfamethazine (4-amino-n-(4,6-dimethyl-2-pyrimidinyl)[14C]benzenesulfonamide) metabolites in the tissues and excreta of swine.

Pigs were given a single oral dose of 14C-sulfamethazine (4-amino-N(I4,6-dimethyl-2-pyrimidinyl)[14C]benzenesulfonamide). Approximately 78% of the 14C was eliminated in the urine and 18% was eliminated in the feces within 192 hr after dosing. The percentage of the 14C remaining in the animals after dosing was as follows: 6 hr, 88%; 24 hr, 49%; 48 hr, 14%; 192 hr, less than 1%. The 14C-labeled compounds in the tissues and excreta were isolated by solvent extraction and by conventional and high-pressure liquid chromatography, and then derivatized and characterized by infrared and mass-spectral analysis. Chemical structures were confirmed by synthesis. The major 14C-labeled compounds in the skeletal muscle, liver and kidney were identified as sulfamethazine, N4-acetylsulfamethazine, the N4-glucose conjugate of sulfamethazine, and N-(4,6-dimethyl-2-pyrimidinyl)benzenesulfonamide (desaminosulfamethazine). The major 14C-labeled compounds in the urine and feces were identified as sulfamethazine and N4-acetylsulfamethazine.