Tissue distribution and elimination kinetics of oxytetracycline in sixteen organs and body fluids were determined in young pigs following intravenous and oral administration. Seventeen non‐fasted pigs, 8–10 weeks of age, weight range 16.4–34.5 kg were dosed intravenously at a dose rate of 11 mg/kg bodyweight. An additional seventeen weaning pigs, 12–14 weeks of age, weight range 27.2–36.3 kg were dosed orally at a dose rate of 48–65 mg/kg bodyweight. Oxytetracycline was rapidly distributed (half‐life, 6.71 ± 1.13 min) in swine. The mean volume of distribution was 1.26 ± 0.18 l/kg and overall body clearance was 3.82 ± 0.59 ml/kg/min. The elimination half‐life of oxytetracycline in pigs was 3.87 ± 0.62 h, which is shorter than has been observed in other domestic animal species. Oxytetracycline became rapidly and efficiently involved in enterohepatic cycling, with as much as 70% of a total intravenous dose being available for reabsorption from the gastrointestinal tract within 1 h after administration. This high degree of enterohepatic recycling prolonged the half‐life, and the large amount of drug that entered the enteric tract contributed to the high volumes of distribution and high k12/k21 ratios. The excellent tissue penetration of this drug further contributed to the high volume of distribution and high k12/k21 ratios obtained. Relationships between plasma and tissue depletion for several major edible organs were found to be statistically significant. Blood plasma is proposed as a body fluid for monitoring oxytetracycline tissue residues.

A pharmacokinetic approach to the delineation of a drug residue profile in food-producing animals has been presented. It is recognized that the determination of a drug withdrawal period is one of the costly developmental procedures in drug development for food animals; thus it is believed that in the early developmental phases, a thorough pharmacokinetic characterization of a drug in the target species would greatly facilitate the design and quality of studies conducted in the later phases of new drug development. It is suggested that drugs that are intended for use in food animals can be characterized kinetically in less costly studies, the results of which might be used to determine the feasibility of developing a drug that might cause serious residue problems. It is also suggested that the pharmacokinetic modeling of a drug in the target animal may provide an essential data base for calculating dosage rates and intervals that directly relate to the efficacy aspects of drug development.

Eighteen non‐fasted, 12–16 week old pigs weighing between 20 and 40 kg were dosed with chloramphenicol intravenously at a dose rate of 22 mg/kg body weight. The pharmacokinetics of chloramphenicol were determined in blood plasma and sixteen selected organs and body fluids. The elimination half‐life in plasma was estimated to be 2.66pL1.06 h and volume of distribution was 1.39pL0.32 I/kg. The body clearance of chloramphenicol was estimated to be 6.64pL1.52 ml/kg/min. The elimination half‐life in tissue was found to range from 1.25 h in kidney to 5.89 h in fat. Most major organs ranged from 2.0 to 5.0 h. Significant correlations were found to exist between plasma concentrations and most major organ concentrations. Chloramphenicol concentrations in muscle, spleen, lung, stomach content, and large intestine content were found to exist slightly beyond the time when concentrations were negative in plasma. However, urine levels exceeded tissue levels at the last slaughter interval. It appears that serum or urine would be a good body fluid for monitoring chloramphenicol residues in tissues, whereas stomach content might be used as an indicator for chloramphenicol treatment for many days after therapy with the drug.

Mature beagles were fed a ground-meal diet containing 0, 2, or 10 μg of oxytetracycline per g for 44 days. The 10-μg/g diet resulted in a shift from a predominantly drug-susceptible population of enteric lactose-fermenting organisms to a multiply antibiotic-resistant population which peaked at 78% resistant organisms. Since a shift to drug-resistant organisms did not occur in the group fed 2 μg/g, the level of oxytetracycline that results in increased incidence of antibiotic resistance lies between 2 and 10 μg/g in this dog model. Rats and hamsters fed diets containing oxytetracycline (10 μg/g or greater) or dihydrostreptomycin (10 μg/g), and provided suspensions of drug-susceptible Escherichia coli , did not develop a population of antibiotic-resistant organisms.

The toxicity of a commercial blend of polybrominated biphenyls was determined in 24 pregnant Holstein heifers that were allotted randomly to one of four experimental groups given 0, .25, 250, or 25,000 mg/day of fire-Master BP-6. The polybrominated biphenyls were mixed with finely ground corn and given by bolus for 60 days or until the animal became moribund. Average body weight of heifers at onset of experiment was 381 kg. No clinical signs of toxicosis were evident in heifers fed 0, .25 or 250 mg/day. Toxicosis was induced in heifers fed 25,000 mg/day resulting in reduced dry matter intake, body weight, heart rate, and respiration rate. Clinical signs were anorexia, emaciation, dehydration, excessive lacrimation and salivation, diarrhea, depression, and abortion or fetal death. All heifers fed 25,000 mg/day became moribund within 33 to 66 days.