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Oxytetracycline (OTC) was administered by constant IV infusion to 3 healthy postpartum cows at rates predicted to approach a steady-state plasma concentration of 5 micrograms/ml. After 8 hours of constant IV infusion, genital tissues were surgically removed. The mean plasma-to-tissue ratios of concentrations of OTC were 0.95, 1.33, 1.88, and 1.04 (2 cows only) for caruncles, endometrium, uterine wall, and ovaries, respectively. Differences between the ratios of any 2 of the uterine tissues were statistically significant (P less than 0.05). Intrauterine (IU) infusions of 5.5 mg of OTC/kg were administered to 3 healthy postpartum cows and 3 postpartum cows with metritis. The mean values of the fraction of the drug absorbed from the uteri of cows given IU infusions of OTC were 0.50 and 0.23 for healthy postpartum cows and postpartum cows with metritis, respectively. Concentrations of OTC were high in the caruncles and endometrium of all cows at 24 hours after IU infusions of the drug. Concentrations in the plasma, uterine wall, and ovaries were low, with mean concentrations of OTC in these tissues in postpartum cows with metritis being lower than those in the same tissues of healthy postpartum cows. Computer-simulated genital tissue concentrations of OTC after twice daily IV doses of 11 mg/kg indicated that this dosage regimen would provide postpartum uterine tissue concentrations greater than 5 micrograms/g throughout the dosage interval in all tissues, except the uterine wall.

A field trial was conducted to determine the efficacy of theophylline in relieving respiratory distress associated with bovine respiratory disease complex (shipping fever). Theophylline (as aminophylline capsules) was administered PO at a dosage of 28 mg/kg of body weight daily for 3 days to 20 calves with naturally acquired disease. Twenty similarly affected calves from the same group were given a placebo, and all calves were administered antibiotics concurrently. Respiratory rate and rectal temperature decreased and physical appearance improved in both groups of calves and was attributed to antibiotic administration or to natural remission of the disease. Five of the calves administered theophylline died; however, no calves administered the placebo died. Plasma theophylline concentration was greatly increased, compared with that determined in clinically normal calves in a pilot study. Bovine respiratory tract disease and/or concurrent antibiotic administration appear to cause such a rapid accumulation of lethal concentration of theophylline that its use should be restricted to hospitals capable of monitoring plasma theophylline concentration.

Previously determined pharmacokinetic parameters of the disposition of oxytetracycline (OTC) in cows were used to predict an IV priming dose and a rate of constant IV infusion of OTC sufficient to approach steady-state equilibrium of the drug between plasma and genital tissue concentrations in healthy postpartum cows and postpartum cows with endometritis. After 8 hours' constant IV infusion at rates calculated to maintain a plasma concentration of approximately 5 micrograms/ml, the mean concentrations of OTC in plasma (microgram/ml) and tissues (microgram/g) of healthy and infected postpartum cows, respectively, were: plasma, 4.95 and 5.23; uterine tissue, 3.65 and 4.18; and ovarian tissue, 4.57 and 4.53. The mean plasma to genital tissue ratios for healthy and infected postpartum cows, respectively, were 1.38 and 1.31 for uterine tissue and 1.09 and 1.16 for ovarian tissue. There were no significant differences (P greater than 0.28) between healthy and infected postpartum cows in any of the parameters investigated. However, plasma-to-genital tissue ratios of concentrations of OTC in postpartum cows as a group were significantly higher (P less than or equal to 0.03) than those previously determined in cycling cows. Computer-simulated uterine tissue concentrations of OTC, after twice daily IV doses of 11 mg of OTC/kg of body weight, indicated that this dosage regimen would provide postpartum uterine tissue concentrations greater than 5 micrograms/g during most of the dosage interval.