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R F Bevill

Publications and source records attributed to R F Bevill.

45 records · Page 3Linked to original sources

Disposition of sulfonamides in food-producing animals IV: Pharmacokinetics of sulfamethazine in cattle following administration of an intravenous dose and three oral dosage forms.

The plasma and urine data obtained following intravenous administration of sulfamethazine to cattle were fit to a one-compartment pharmacokinetic model with a half-life of elimination of 9 hr and a volume of distribution of 0.35 liter/kg. Sulfamethazine was eliminated by excretion of unchanged sulfamethazine (18%) into urine and by formation of three metabolites subsequently excreted into urine. Sulfamethazine also was administered as a solution, a rapid-release bolus, and a sustained-release bolus. The change in the urinary metabolic pattern with different routes of administration suggested that first-pass metabolism was occurring during the absorption process. The absorption half-life was 6 hr. The absorption process for the two solid boluses kinetically appeared to include a dissolution step.

Administration, Oral↗

Disposition of sulfonamides in food-producing animals V: Disposition of sulfathiazole in tissue, urine, and plasma of sheep following intravenous administration.

The plasma, urine, and tissue sulfathiazole concentrations were determined at various times following intravenous administration to 12 sheep. The plasma and urine data were consistent with a one-compartment pharmacokinetic model, with an elimination half-life of 1.1 hr and a volume of distribution of 0.39 liter/kg. Sulfathiazole was eliminated by excretion of unchanged drug in urine (67%) and by formation of two metabolites. The data obtained from eight tissue sites were consistent with the one-compartment pharmacokinetic model presented and confirmed that tissue residues of sulfathiazole can be calculated from serum and urine drug concentration.

Animals↗

High-pressure liquid chromatographic determination of tetracyclines in urine.

The quantitation of oxytetracycline, tetracycline, and chlortetracycline was accomplished by high-pressure liquid chromatography using an anion-exchange column. The tetracyclines were extracted from urine as their calcium complexes. Concentrations as low as 12 microgram of oxytetracycline/ml and 4 microgram of tetracycline and chlortetracycline/ml were quantitated accurately. The relative standard deviation of the method varied from 0 to 5%.

Animals↗

Disposition of sulfonamides in food-producing animals: pharmacokinetics of sulfamethazine in lambs.

Previously reported plasma and urine concentrations of unchanged sulfamethazine and 3 metabolites following intravenous administration of sodium sulfamethazine to young ewe lamb were fitted to a linear pharmacokinetic model in which sulfamethazine itself obeyed 1-compartment phamacokinetics. The average rate constant for overall elimination of sulfamethazine was 0.096 +/- 0.023 hours-1, corresponding to a biological half-life of 7.2 +/- 1.7 hours. The results of residue analysis of 8 tissues obtained at slaughter showed that tissue and plasma concentrations and urine output of unchanged sulfamethazine fell parallel throughout the experiment. The results indicate that determination of the plasma concentration or urinary output of sulfamethazine can be substituted for tissue residue analysis to determine contamination of carcasses above specified tolerance limits.

Animals↗

Disposition of sulfonamides in food-producing animals: concentrations of sulfamethazine and its metabolites in plasma, urine, and tissues of lambs following intravenous administration.

A sensitive, precise, and efficient analytical method for sulfamethazine in the liver, kidney, heart, skeletal muscle, and fat of lambs is reported. The method involves freezing cubed tissue in liquid nitrogen, powdering the frozen tissue in a liquid nitrogen-cooled blender, and extracting the tissue on a sodium sulfate column with chloroform:acetone. A thin-layer chromatographic procedure capable of separating and quantitating sulfamethazine and 3 metabolites (acetyl, hydroxylated, and polar conjugate(s) in lamb urine is also reported. Sulfamethazine was administered intravenously (107.25 mg/kg body weight) to 14 cross-bred ewe lambs. The concentration of sulfamethazine in plasma and tissues and sulfamethazine and its metabolites in urine were determined in samples collected at specific postdosing times. The concentration of sulfamethazine in plasma exceeded 5 mg/100 ml for 18 to 24 hours after drug administration. The excretion of diazotizable materials in the urine was essentially complete at the 60th hour after dosing. The drug was excreted in the urine as sulfamethazine, a hydroxylated metabolite, acetylsulfamethazine, and polar conjugate(s). Tissue concentrations of the drug were greatest in the kidney and less (in decreasing quantities) in liver, heart, skeletal muscle, body fat, and omental fat.

Animals↗

Disposition of sulfonamides in food-producing animals: pharmacokinetics of sulfathiazole in sheep.

Plasma and urine data on sheep following administration of sulfathiazole as single intravenous and oral doses were examined. A one-compartment open model was developed to describe the pharmacokinetics of sulfathiazole in sheep. The drug was rapidly eliminated, primarily by renal excretion of unchanged sulfathiazole and metabolism to acetyl sulfathiazole, with a biological half-life of 1.3 hours. Sulfathiazole was absorbed slowly (half-life, 18 hours) and relatively completely (73%) after oral administration in solution.

Administration, Oral↗

High-pressure liquid chromatographic separation, identification, and determination of sulfa drugs and their metabolites in urine.

A high-pressure liquid chromatographic method for the separation and quantitative determination of sulfamethazine, sulfathiazole, and their N4-acetylated metabolites on an amino-bonded reversed-phase column was developed. The method is suitable for the analysis of these compounds in pure solutions as well as in cattle urine. Retention times were reproducible. Injection volumes containing 0.2 mug of individual sulfonamides or their acetyl derivatives were successfully quantitated; coefficients of variation ranged from 0 to 0.073 for individual sulfonamides.

Acetylation↗

Effect of a polychlorinated biphenyl mixture on swine reproduction and tissue residues.

A commercial polychlorinated biphenyl (PCB) mixture containing 42% chlorine by weight was fed at the dose level of 20 ppm to 3rd-litter sows throughout gestation and nursing. Treated sows differed significantly (0.05% level) from control sows in the number of live pigs they farrowed. Treated sows also had more mummified fetuses. Performance of live-born pigs was not affected by feeding PCB to the sows during nursing. Pathologic changes in the sows included hypertrophy of liver and erosion of stomach. Two treated sows, 1 of which did not conceive, had signs of extensive chronic septicemia. Slight atrophy of spleen and thyroid gland was observed in pigs from treated sows. Blood and tissue residues of PCB were less than 0.5 ppm in both sows and pigs, but the relative amounts of PCB components varied among sows and pigs, as well as among tissues. Fat concentrations of total PCB in sows ranged from 4 to 20 ppm and those of component residues varied from 0 to 60 ppm.

Adipose Tissue↗

The formation, disposition, and hepatic metabolism of dimethylnitrosamine in the pig.

The disposition, metabolism, and endogenous formation of N-nitrosodimethylamine (NDMA) from nitrosatable precursors was studied in the intact pig and in animals with cannulated hepatic and portal veins and catheterized bile ducts. Rates of disappearance of NDMA from peripheral venous and arterial blood after iv injections were virtually identical and the compound appeared in bile after a lag time of about 1 hr, with a subsequent decline in biliary concentration at about the same rate as in circulating blood. Measurements of NDMA in portal and hepatic vein blood after oral doses of 10, 1.0 and 0.1 mg/kg, respectively, showed progressively greater hepatic extraction with levels in the hepatic vein approaching the limits of detection after the lowest dose. Both halothane and ethanol virtually abolished the hepatic extraction of NDMA, presumably due to their known inhibitory action on its metabolism in the liver. Endogenous formation of NDMA and N-nitrosomorpholine after oral doses of the amines plus nitrite was demonstrated by their detection and measurement in the portal vein blood. Morpholine was nitrosated more effectively than dimethylamine and inhibited the nitrosation of the latter when the two amines were given together. NDMA was found in the portal blood after sequential oral administration of aminopyrine and nitrite, the concentration being considerably greater after fasting for 24 hr than after a 2-hr fast when much food was present in the stomach.

Aminopyrine↗