The disposition of theophylline in healthy ruminating calves was best described by a first-order 2-compartment open pharamacokinetic model. The drug had a mean elimination half-life of 6.4 hours and a mean distribution half-life of 22 minutes. Total body clearance averaged 91 ml/kg/h. The mean values for the pharmacokinetic volume of the central compartment, pharmacokinetic volume of distribution during the terminal phase, and volume of distribution at steady state were 0.502, 0.870, and 0.815 L/kg, respectively. Theophylline was readily absorbed after oral administration to the ruminating calf, with a mean fraction of 0.93 absorbed. The plasma concentrations after oral dosing peaked in approximately 5 to 6 hours, with a mean absorption half-life of 3.7 hours. A flip-flop model (rate constant of input is much smaller than the rate constant of output) of drug absorption was not found because the elimination process roughly paralleled that of the study concerning IV administration. In a multiple-dose trial that used a dosage regimen based on single-dose pharmacokinetic values, clinically normal calves responded as predicted. However, diseased calves had higher than expected plasma concentrations after being given multiple oral doses of theophylline at 28 mg/kg once daily. Overt signs of toxicosis were not seen, but this aspect of the drug was not formally investigated. Theophylline can be used as an ancillary therapeutic agent to treat bovine respiratory disease, but not without risk. The suggested oral dose of theophylline at 28 mg/kg of body weight once daily should be tailored to each case. Twice daily oral dosing at 20 mg/kg should reduce the plasma peak:trough ratio and provide plasma concentrations more cnsistently within the human therapeutic range of 10 to 20 micrograms/ml. Even then, therapeutic drug monitoring should be done.

A controlled anthelmintic trial was conducted to determine the efficacy of febantel paste (45.5%) at dosages of 2.5, 5.0, 7.5, and 10.0 mg/kg in calves harboring natural gastrointestinal nematode infections. Dosages of 5.0, 7.5 and 10.0 mg of febantel/kg of body weight were greater than 96% effective in removing adults of Haemonchus contortus, Ostertagia spp, Cooperia spp, and Oesophagostomum radiatum. The 2.5 mg/kg dosage was considered suboptimal because of low efficacy against Ostertagia and Cooperia spp. Efficacies against Trichostrongylus axei, Trichuris spp, Bunostomum phlebotomum, and Strongyloides papillosus were difficult to determine because fewer numbers of these nematodes were recovered. Efficacies of febantel paste against immature bovine parasites ranged from 83.62% to 97.72%.

Antiparasitic efficacy of ivermectin against migrating Gasterophilus intestinalis was evaluated in 36 treated and 24 nontreated (n = 12) or vehicle-treated (n = 12) ponies experimentally and naturally infected with G intestinalis and naturally infected with G nasalis. Each pony was experimentally infected with 500 G intestinalis lst instars in 2 divided doses on days -14 and -7 before treatment. On day 0, ivermectin was administered at the rate of 200 microgram/kg of body weight by IV (n = 12) or IM injection (n = 12) or given as an oral paste (n = 12). Ponies were euthanatized and necropsied 21 days after treatment. In each nontreated or vehicle-treated pony, late lst-, lst- to 2nd-instar molt, and early 2nd-instars of G intestinalis were found in the mouth, and 2nd- and 3rd instars of G intestinalis and 3rd instars of G nasalis were found in the stomach. Bots were not found in any ivermectin-treated pony and, thus, ivermectin was 100% effective against oral and gastric stages. Adverse reactions were not observed in ponies given ivermectin by IM injection or orally, but 1 pony given the vehicle IV and 1 pony given ivermectin (in the vehicle) IV had an anaphylactic reaction, resulting in death of the ivermectin-treated pony. It was speculated that the adverse reaction was caused by histamines released in response to vehicle components given by IV injection.

A 2 X 2 crossover design trial was conducted in gilts to determine the bioavailability and pharmacokinectics of tetracycline hydrochloride. The bioavailability of tretracycline hydrochloride administered orally to fasted gilts was approximately 23%. After intravascular administration, the disposition kinetics of tetracycline in plasma were best described by a triexponential equation. The drug had a rapid distribution phase followed by a relatively slow elimination phase, with half-life of 16 hours. Its large volume of distribution (4.5 +/- 1.06 L/kg) suggested that tetracycline is distributed widely in swine tissues. Total body clearance was 0.185 +/- 0.24 L/kg/h. Other pharamacokinectic variables were estimated. In a second trial, 3 gilts were fed a ration containing 0.55 g of tetracycline hydrochloride/kg of feed. Resulting plasma concentration of tetracycline was determined at selected times during 96 hours after exposure to the medicated feed. Plasma drug concentration peaked (0.6 microgram/ml) at 72 hours after access to the medicated feed.

Norfloxacin, a 4-quinolone antibiotic, was administered orally to 4 healthy dogs at dosages of 11 and 22 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) norfloxacin concentrations were measured at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after the first and seventh dose of each dosing regimen. When administered at a dosage of 11 mg/kg, the mean peak serum concentration (Cmax) was 1.0 micrograms/ml at 1 hour, the time of mean peak concentration (Tmax) after the first dose. After the seventh dose, the Cmax was 1.4 micrograms/ml at Tmax of 1.5 hours. The Tmax for the TCF concentration was 5 hours, with Cmax of 0.3 micrograms/ml and 0.7 micrograms/ml after the first and seventh dose, respectively. When administered at a dosage of 22 mg/kg, the serum Tmax was 2 hours after the first dose, with Cmax of 2.8 micrograms/ml. After the seventh dose, the serum Tmax was 1.5 hours, with Cmax of 2.8 micrograms/ml. The Tmax for the TCF concentration was 5 hours after the first and seventh doses, with Cmax of 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. After the seventh dose, the serum elimination half-life was 6.3 hours for a dosage of 11 mg/kg and was 6.7 hours for a dosage of 22 mg/kg. For serum concentration, the area under the curve from 0 to 12 hours (AUC0 leads to 12) was 8.77 micrograms.h/ml and 18.27 micrograms.h/ml for dosages of 11 mg/kg and 22 mg/kg, respectively. The corresponding AUC0 leads to 12 for the TCF concentration was 6.20 micrograms.h/ml and 16.42 micrograms.h/ml. The percentage of TCF penetration (AUC(TCF)/AUCserum) was 71% at a dosage of 11 mg/kg and 90% at a dosage of 22 mg/kg.

Influence of supplemental Se on humoral immune response was measured in 60 weaned beef calves with marginal blood Se status. Calves were fed a Se-deficient diet consisting of corn silage, corn grain, and soybean meal. Blood Se concentrations, primary and secondary humoral immune responses to hen egg lysozyme inoculation, and weight gain were determined in a 70-day trial. Calves fed 20 mg of Se/kg of mineral mixture ad libitum had lower antibody responses (P less than 0.02), compared with calves fed 20 mg of Se/kg of mineral mixture and given 0.1 mg of Se and 0.22 IU of vitamin E/kg of body weight, IM, or with calves fed 80, 120, 160, or 200 mg of Se/kg of mineral mixture. Calves fed 80, 120, 160, or 200 mg of Se/kg of mineral mixture had higher (P less than 0.001) blood Se concentrations on day 70, compared with calves fed 20 mg of Se/kg of mineral mixture and given 0.1 mg of Se and 0.22 IU of vitamin E/kg of body weight, IM. Selenium supplementation had no effect on weight gain.

Six groups of 5 dogs each were fed dilutions of canine adenovirus-2, either as raw liquid or after insertion into cornmeal baits. By the fourth week after vaccination, 29 of the 30 dogs developed high titers of serum-neutralizing antibodies to the virus.

Male Holstein calves were each inoculated with 350,000 sporulated oocysts of Eimeria bovis. Two calves were given decoquinate (0.5 mg/kg of body weight) continuously in dry feed for 29 days, and 2 calves each were given 0.5, 1, or 1.5 mg of decoquinate/kg on an every 2nd-or 3rd-day schedule for 29 days. Calves given decoquinate continuously did not discharge oocysts but had slightly loose feces. In general, the number of oocysts discharged increased and fecal consistency decreased as the time between feeding of medicated feed increased. Calves given 0.5 or 1.5 mg of decoquinate/kg every 3rd day discharged more oocysts and had more diarrhea than did calves given 1 mg of decoquinate/kg every 3rd day. At postinoculation day 29, calves were euthanatized. At necropsy, intestinal tissues of calves given decoquinate were mostly normal. Apparently, reduced infections along with the elapsed time were sufficient to resolve most intestinal lesions caused by the coccidia. Decoquinate was most effective when fed continuously at 0.5 mg/kg. However, when fed at 1 or 1.5 mg of decoquinate/kg every 2nd day or 1.5 mg of decoquinate/kg every 3rd day, oocyst production was reduced and clinical coccidiosis was prevented.

Serum concentrations of iodine were determined after cattle were given ethylenediamine dihydriodide (EDDI) orally at dosages ranging from 0.0 (placebo) to 0.77 mg/kg of body weight/day. The serum iodine concentration was correlated with the dosage of EDDI. A rate of 0.11 mg EDDI/kg/day was correlated with serum iodine concentrations (20 to 80 micrograms/dl) previously found to be effective in preventing foot rot in cattle. A linear dose-response curve that was generated could be helpful in predicting dosage of EDDI if the serum iodine concentration is known.

The disposition of theophylline in healthy ruminating calves was best described by a first-order 2-compartment open pharamacokinetic model. The drug had a mean elimination half-life of 6.4 hours and a mean distribution half-life of 22 minutes. Total body clearance averaged 91 ml/kg/h. The mean values for the pharmacokinetic volume of the central compartment, pharmacokinetic volume of distribution during the terminal phase, and volume of distribution at steady state were 0.502, 0.870, and 0.815 L/kg, respectively. Theophylline was readily absorbed after oral administration to the ruminating calf, with a mean fraction of 0.93 absorbed. The plasma concentrations after oral dosing peaked in approximately 5 to 6 hours, with a mean absorption half-life of 3.7 hours. A flip-flop model (rate constant of input is much smaller than the rate constant of output) of drug absorption was not found because the elimination process roughly paralleled that of the study concerning IV administration. In a multiple-dose trial that used a dosage regimen based on single-dose pharmacokinetic values, clinically normal calves responded as predicted. However, diseased calves had higher than expected plasma concentrations after being given multiple oral doses of theophylline at 28 mg/kg once daily. Overt signs of toxicosis were not seen, but this aspect of the drug was not formally investigated. Theophylline can be used as an ancillary therapeutic agent to treat bovine respiratory disease, but not without risk. The suggested oral dose of theophylline at 28 mg/kg of body weight once daily should be tailored to each case. Twice daily oral dosing at 20 mg/kg should reduce the plasma peak:trough ratio and provide plasma concentrations more cnsistently within the human therapeutic range of 10 to 20 micrograms/ml. Even then, therapeutic drug monitoring should be done.