Pharmacokinetics, renal clearance, tissue distribution, and residue aspects of sulphadimidine and its N₄‐acetyl metabolite in pigs

Abstract

Pharmacokinetics and tissue distribution experiments were conducted in pigs to which sulphadimidine (SDM) was administered intravenously, orally, and intramuscularly at a dosage of 20 mg SDM/kg. SDM was acetylated extensively, but neither hydroxy metabolites nor their derivatives could be detected in plasma, edible tissues or urine. Following i.v. and two oral routes of administration, the N4-acetylsulphadimidine (N4-SDM) concentration-time curve runs parallel to that of SDM. The percentage of N4-SDM in plasma was in the range between 7 and 13.5% of the total sulphonamide concentration. The bioavailability of SDM administered in a drench was 88.9 +/- 5.4% and administered mixed with pelleted feed for 3 consecutive days it was 48.0 +/- 11.5%. The renal clearance of unbound SDM, which was urine flow related, was 1/7 of that of creatinine, indicating reabsorption of the parent drug. The unbound N4-SDM was eliminated three times faster than creatinine, indicating that tubular secretion was the predominant mechanism of excretion. After i.v. administration, 51.9% of the administered dose was recovered in urine within 72 h p.i., one quarter of which as SDM and three quarters as N4-SDM. Tissue distribution data obtained at 26, 74, 168, and 218 h after i.m. injection revealed that the highest SDM concentration was found in plasma. The SDM concentration in muscle, liver, and kidney ranged from one third to one fifth of that in plasma. The N4-SDM formed a minor part of the sulphonamide content in edible tissues, in which the SDM as well as the N4-SDM concentration parallelled the plasma concentrations. Negative results obtained with a semi-quantitative bioassay method, based on monitoring of urine or plasma, revealed that the SDM concentration levels in edible tissues were in that case below 0.1 mu/g tissue.

Application of an enzyme immunoassay for the determination of sulphamethazine (sulphadimidine) residues in swine urine and plasma and their use as predictors of the level in edible tissue

“…Compared with the tissue-urine ratios, the tissue-plasma ratios showed less variation. This was also observed by Nouws et al (1986a) and Randecker et al (1987).…”

“…Compared with the concentrations in the tissue samples, the concentration in plasma was 2-4 times higher. This compares with the results of Nouws et al (1986a) in which they found that the sulphamethazine concentration in muscle, liver and kidney ranged from one-third to one fifth of that in plasma. It was noticeable that between the mean sulphamethazine concentrations in tissue and plasma obtained after 4 days versus 7 days drug withdrawal, no obvious differences were observed (see table 1).…”

“…An inhibition zone with a diameter of 20 mm (including the disc with a diameter of 12-7 mm) is applied as the action level. At inhibition zones of <20mm obtained with the NDKT with plasma, urine and renal pelvis fluid examination, the level in tissues should be less than 200 ug/kg for sulphamethazine and less than 100 ug/kg for sulphadimethoxine, sulphadiazine and sulphadoxine (Nouws et al 1986a(Nouws et al , 1988. In practice, the inhibition zone obtained with renal pelvis fluid is used as a predictor of sulphonamide levels in swine tissues.…”

The effect of dietary nitrite and nitrate on the metabolism of sulphadimidine administered orally to pigs

“…In the absence of nitrate or nitrite, the plasma concentrations of SDM and N4-acetyl-SDM were similar to those previously reported by other authors (4,8).…”

Bioconcentration and Elimination of Sulfamethazine and Its Main Metabolite in Sturgeon (Acipenser schrenkii)

“…Sulfamethazine is known to undergo metabolism to mainly form N 4 -acetyl-SM 2 in numerous species of domestic animals, including fish and humans (10)(11)(12)(13)(14). Metabolic alteration of the parent compound by fish to more polar species or to less polar species can have an impact upon bioconcentration (5), so N 4 -acetyl-SM 2 , which is less polar than SM 2 , was used as a biodegradation marker of the drug in the test organism.…”