METABOLISM OF C-14 SULPHADIMETHOXANE IN SWINE

1. C-14-sulphadimethoxine thoxy-4-pyrimidinyl)benzene-[U-C-14]-sulphon amide; C-14-SDM) was given orally (60 mg/kg body weight) to eight swin e (weight 27-32 kg). Urine and faeces were collected from 0 to 72 h af ter dosing and tissue samples were collected from animals exsanguinate d at 12, 24, 48 and 72 h after dosing. The concentration of total C-14 -labelled residues (C-14-SDM equivalents) in tissues other than the ga strointestinal tract ranged from 99.1 ppm (plasma) to 13.8 ppm (adipos e tissue) 12 h after dosing. Seventy-two hours after dosing tissue con centrations 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 C-14, 77% was excreted in the urine from 0 to 72 h after dosing with C-14-SDM, mostly in the 0-24-h collection. F ifteen percent was excreted in the faeces from 0 to 72 h after dosing, with most of this occurring 36-72 h post-dosing. 3. C-14-SDM accounte d for 24% (liver) to 66% (adipose tissue) and the N-4-acetyl derivativ e of SDM (N-4-Ac-SDM) accounted for 10% (skeletal muscle) to 35% (kidn ey) of the total C-14 in the tissues 12 h after dosing. The N-4-glucos e conjugate of SDM (G-SDM) was a major C-14-labelled compound in skele tal muscle (21% of total) and liver (28%) but it was not detected in a dipose tissue or kidney. The N-4-glucuronic acid conjugate of SDM (GA- SDM) was a minor metabolite in kidney, but was not detected in other t issues collected 12 h after dosing. Desamino SDM was a minor metabolit e in the kidney. A minor metabolite in plasma was identified as the su lphate ester of 3-hydroxysulphadimethoxine. 4. C-14-labelled fractions isolated from 0 to 6-h urine included N-4-Ac-SDM (82%), SDM (3%) and GA-SDM (6%).