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ARS Home » Plains Area » Fargo, North Dakota » Edward T. Schafer Agricultural Research Center » Food Animal Metabolism Research » Research » Publications at this Location » Publication #63950


item Feil, Vernon
item Paulson, Gaylord

Submitted to: Xenobiotica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/14/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: Sulphadimethoxine (SDM) is an antibiotic that has been approved for use in chickens, turkeys, cattle, dogs, cats, horses and certain fish, but it has not been approved for use in swine. However, because SDM is readily available (for approved use in other species), there is concern that this antibiotic is (or will be) used in swine. Therefore, it is important to know how swine get rid of SDM when they are exposed to this compound, especially as it relates to developing methods to analyze swine tissues for SDM related residues. The studies reported here were conducted using carbon-14 labeled SDM. The use of this radiotracer technique made it possible to more completely assess how SDM is handled in swine than was possible with less sophisticated, techniques used in earlier investigations. The studies reported here demonstrated that SDM was converted to several unique compounds (not previously described) and that these compounds were present in liver, kidney, skeletal muscle and excreta from swine dosed with SDM. The information resulting from these studies is especially useful for regulatory agencies (e.g. Food and Drug Administration and Animal and Plant Health Inspection Service) who are responsible for insuring that the food supply is safe for human consumption.

Technical Abstract: 14C-Sulphadimethoxine (4-amino-N-(2,6-dimethoxy-4- pyrimidinyl)benzene-[U-14C]-sulphonamide; 14C-SDM) was given orally to eight swine. Urine and faeces were collected from 0-72 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- labeled 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 h after dosing tissue concentrations ranged from 5.4 ppm (plasma) to 0.5 ppm (skeletal muscle). Seventy seven % of the 14C-activity was excreted in the urine from 0-72 h after dosing with 14C-SDM. Fifteen % was excreted in the faeces from 0-72 h after dosing. 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-labeled 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 urine and kidney, but it was not detected in other tissues. Desamino SDM was a minor metabolite in the kidney. A minor metabolite in plasma was identified as the sulfate ester of 3-hydroxysulphadimethoxine. 14C- Labeled fractions isolated from 0-6 h urine included N4-Ac-SDM (82%), SDM (3%) and GA-SDM (6%)