Metabolism of 14C-sulphadimethoxane in swine.

1. 14C-sulphadimethoxine (4-amino-N-(2,6-dimethoxy-4-pyrimidinyl)benzene-[U-14C]-sulphonamide; 14C-SDM) was given orally (60 mg/kg body weight) to eight swine (weight 27-32 kg). Urine and faeces were collected from 0 to 72 h after dosing and tissue samples were collected from animals exsanguinated at 12, 24, 48 and 72 h after dosing. The concentration of total 14C-labelled residues (14C-SDM equivalents) in tissues other than the gastrointestinal tract ranged from 99-1 ppm (plasma) to 13.8 ppm (adipose tissue) 12 h after dosing. Seventy-two hours after dosing tissue concentrations ranged from 5.4 ppm (plasma) to 0.5 ppm (skeletal muscle). The concentration in the large intestine was substantially higher (10.4 ppm) than in the stomach (2.8 ppm) and small intestine (1.4 ppm) 72 h after dosing. 2. Of the 14C, 77% was excreted in the urine from 0 to 72 h after dosing with 14C-SDM, mostly in the 0-24-h collection. Fifteen percent was excreted in the faeces from 0 to 72 h after dosing, with most of this occurring 36-72 h post-dosing. 3. 14C-SDM accounted for 24% (liver) to 66% (adipose tissue) and the N4-acetyl derivative of SDM (N4-Ac-SDM) accounted for 10% (skeletal muscle) to 35% (kidney) of the total 14C in the tissues 12 h after dosing. The N4-glucose conjugate of SDM (G-SDM) was a major 14C-labelled compound in skeletal muscle (21% of total) and liver (28%) but it was not detected in adipose tissue or kidney. The N4-glucuronic acid conjugate of SDM (GA-SDM) was a minor metabolite in kidney, but was not detected in other tissues collected 12 h after dosing. Desamino SDM was a minor metabolite in the kidney. A minor metabolite in plasma was identified as the sulphate ester of 3-hydroxysulphadimethoxine. 4. 14C-labelled fractions isolated from 0 to 6-h urine included N4-Ac-SDM (82%), SDM (3%) and GA-SDM (6%).