The growth hormone (GH) secretagogue activity of variable dosages of clonidine (16.5, 50, 150, and 450 microgram/kg of body weight), given orally mixed with the daily food ration, was evaluated in young and old dogs. Significant (P < 0.05) increase in plasma GH concentration was detected at all dosages tested in young dogs and in response to all but the lowest dose tested in the old dogs fed the clonidine-containing diet. Old dogs had plasma GH concentration that exceeded that of young dogs when higher doses of clonidine were used. A clonidine (100 microgram/kg)-supplemented diet was fed to middle-aged dogs twice daily for 30 days. Significant (P < 0.01) increase of plasma GH concentration was observed on the first day of the feeding trial, but was undetectable by day 30. After feeding the clonidine-enhanced diet for 30 days, the effects on thymic morphology were variable, and there was no effect on plasma thymulin titer. Clonidine-fed dogs had significantly increased lymphocyte blastogenic responsiveness to mitogens, compared with that of control dogs, when evaluated as stimulation index.

Six mature Holstein bulls were each given 10 mg of phenylbutazone (PBZ)/kg of body weight, PO. Of the 6 bulls, 3 were given 10 mg of PBZ/kg by rapid IV administration 4 weeks later. Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling (sum of exponential functions). The harmonic mean of the biologic half-life of PBZ was 62.6 +/- 12.9 hours after oral administration and 61.6 +/- 7.2 hours after IV administration. The mean residence time was 94.61 +/- 8.44 hours and 90.49 +/- 8.93 hours for oral and IV administration, respectively. The mean total body clearance was 0.0015 +/- 0.0003 L/h/kg, with the mean apparent volume of distribution 0.134 +/- 0.021 L/kg. Mean bioavailability was 73 +/- 2% after oral administration. Phenylbutazone was adequately absorbed from the gastrointestinal tract in bulls. The apparent volume of distribution was small, indicating that PBZ distributed mainly into plasma and extracellular fluid. The total body clearance was also small, which accounted for the long half-life of PBZ in bulls.

Six mature Holstein bulls were given an 8-day course of phenylbutazone (PBZ) orally (loading dose, 12 mg of PBZ/kg of body weight and 7 maintenance doses of 6 mg of PBZ/kg, q 24 h). Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling. The harmonic mean +/- pseudo-SD of the biologic half-life of PBZ was 61.8 +/- 12.8 hours. The arithmetic mean +/- SEM of the total body clearance and apparent volume of distribution were 0.0021 +/- 0.0001 L/h/kg and 0.201 +/- 0.009 L/kg, respectively. The predicted mean minimal plasma concentration of PBZ with this dosage regimen was 75.06 +/- 4.05 microgram/ml. The predicted minimal plasma drug concentration was compared with the observed minimal plasma drug concentration in another group of bulls treated with PBZ for at least 60 days. Sixteen mature Holstein bulls were given approximately 6 mg of PBZ/kg, PO, daily for various musculoskeletal disorders. The mean observed minimal plasma concentration of PBZ in the 16 bulls was 76.10 +/- 2.04 microgram/ml, whereas the mean predicted minimal plasma concentration was 74.69 +/- 3.10 microgram/ml. Dosages of 4 to 6 mg of PBZ/kg, q 24 h, or 10 to 14 mg of PBZ/kg, q 48 h, provided therapeutic plasma concentrations of PBZ with minimal steady-state concentrations between 50 and 70 microgram/ml.

Clorazepate dipotassium was administered orally to 8 healthy dogs at a dosage of 2 mg/kg of body weight, q 12 h, for 21 days. Serum disposition of nordiazepam, the principle metabolite of clorazepate, was determined after the first and last dose of clorazepate. Disposition variables were analyzed by use of model-independent pharmacokinetics by the predictive equations method and the trapezoidal rule method. Complete blood counts, serum chemical analyses, and urinalyses were performed before administration of clorazepate and at 10 and 21 days after administration of clorazepate. Maximal nordiazepam concentrations ranged from 446 to 1,542 ng/ml (814 +/- 334 ng/ml), at 59 to 180 minutes (97.9 +/- 42.0 minutes) after a single oral dose of clorazepate. Maximal nordiazepam concentrations ranged from 927 to 1,460 ng/ml (1,308 +/- 187.6 ng/ml), at 120 to 239 minutes (153 +/- 57.9 minutes) after multiple oral doses of clorazepate. Serum disposition was significantly altered after multiple doses of clorazepate. Using data determined by the predictive equations method, the mean residence time after multiple doses (712 +/- 214 minutes) was longer (P less than 0.05) than after a single dose (527 +/- 95.8 minutes). Oral volume of distribution after multiple doses of clorazepate (1.76 +/- 0.647 L/kg) was smaller (P less than 0.02) than after a single dose (3.18 +/- 1.52 L/kg). Oral clearance after multiple doses of clorazepate (3.09 +/- 0.726 milliliter/min/kg) was less (P less than 0.001) than after a singledose (6.54 +/- 2.15 ml/min/kg). Absorption half-life after multiple doses (72 minutes) was longer (P less than 0.01) than after a single dose (33 minutes). The elimination half-life after a single dose (284 minutes) was not significantly different after multiple doses (355 minutes). Significant changes (P less than 0.05) in serum chemical values after multiple doses of clorazepate included decreased concentrations of albumin, total protein, and calcium and increased concentrations of urea nitrogen and glucose. Serum activities of alkaline phosphatase and alanine transaminase increased after multiple doses of clorazepate. Significant changes (P less than 0.05) in the hemogram included increased total WBC count, segmented neutrophils, lymphocytes, and eosinophils. Urine pH after multiple doses (5.88 +/- 0.641) was lower (P less than 0.01) than after a single dose (7.44 +/- 1.29). All changes in laboratory values remained within our reference ranges. Mild sedation and ataxia developed in only 1 dog after the first dose of clorazepate. These effects were transient and did not redevelop with additional dosing. An oral clorazepate dosage of 2 microgram/kg, q 12 h, maintains serum nordiazepam concentrations considered to be therapeutic in human beings (500 to 1,900 ng/ml).

A specific thromboxane synthetase inhibitor, 3-methyl-2 (3-pyridyl)-1-indoleoctanoic acid (CGS 12970) was administered orally to 6 healthy adult Beagles at a dosage of 30 mg/kg of body weight. Blood generation of thromboxane B2 and urinary excretion of thromboxane B2 were measured before and after administration of CGS 12970. Although 97 +/- 0.4% inhibition of thromboxane B2 generation was observed within 2 hours after a single dose of CGS 12970 was administered orally, an effect on urinary excretion of thromboxane B2 was not observed. Additionally, oral administration of 30 mg/kg every 12 hours resulted in 80 +/- 14% inhibition of thromboxane B2 generation but had no effect on urinary thromboxane B2 excretion.

Disposition kinetics of cloxacillin were examined in calves after topical administration of benzathine cloxacillin and single IV administration of sodium cloxacillin, and the susceptibility of 17 field isolates of Moraxella bovis was measured. For the IV pharmacokinetic phase, sodium cloxacillin was administered at dosage of 10 mg/kg of body weight to male Holstein calves (n = 6, weighing 146 to 170 kg), and serum concentration of cloxacillin was measured thereafter for 10 hours. For the ocular pharmacokinetic phase, 6 calves were given either of 4 benzathine cloxacillin topical formulations consisting of 50-, 125-, 250-, or 375-mg doses. Treatment was repeated every 10 days until all 4 benzathine cloxacillin dosages were tested in the same 6 calves. Blood and tears were collected for 72 hours after each benzathine cloxacillin formulation was administered, and the concentration of cloxacillin in each specimen was measured, using a bioassay. The minimal inhibitory concentration of cloxacillin for 17 field isolates of M bovis was determined by use of an agar pour-plate dilution assay. After single IV administration of sodium cloxacillin, its half-life, body clearance, and volume of distribution were 19.5 +/- 12.8 minutes, 18.3 +/- 2.2 ml/min.kg, and 496 +/- 290 ml/kg, respectively. After topical administration of benzathine cloxacillin, cloxacillin concentration in lacrimal fluid peaked between 30 and 45 minutes and ranged between 963 microgram/ml and 3,256 microgram/ml for the 125- and 375- mg doses, respectively. There was no detectable cloxacillin activity in the lacrimal fluid of any calf by 36 hours after topical administration of benzathine cloxacillin, and cloxacillin was not detected in the serum at any time. The mean lacrimal fluid cloxacillin concentration for the 4 groups during the first 8 hours was not significantly different; however, by 12 hours, the cloxacillin concentration in tears from calves of the 250- and 375-mg groups was significantly (P < 0.05) greater than that in calves of the 50- and 125-mg groups. Cloxacillin concentration greater than or equal to 3.13 microgram/ml was maintained for a significantly (P < 0.05) longer time after treatment, using the 375-mg dose, compared with the 50-mg dose of benzathine cloxacillin. The minimal inhibitory concentration of cloxacillin for 1 isolate was 6.25 microgram/ml, but was less than or equal to 3.13 microgram/ml for 16 other M bovis isolates.

Ceftiofur hydrochloride was tested for effectiveness against induced colibacillosis in neonatal swine. In this model, pigs < 12 hours old were inoculated via stomach tube with a virulent, K99+, nalidixic acid-resistant strain of Escherichia coli. Six hours after challenge exposure, 1 dose of ceftiofur was administered either IM or orally in experiment 1 and orally only in experiment 2. Mortality, shedding of bacteria, fecal consistency scores, and body weight changes were monitored for 10 days. In experiment 1 (n = 383 pigs), all treatments at dosage that ranged between 0.5 and 64.0 mg of ceftiofur/kg of body weight significantly (P < 0.001) reduced mortality, bacterial shedding, and diarrhea and increased weight gain, compared with findings in untreated controls. There were no detectable differences between oral and IM routes, except that there was greater reduction in bacteria shedding associated with the oral route of administration. In experiment 2 (n = 505 pigs), ceftiofur was administered orally either once at 6 hours after challenge exposure or twice at 6 and at 48 hours after the first dose. Dosage of ceftiofur was 0, 5, 10, 20, 30, or 60 mg/kg administered once, or half the same dose was administered at each of 2 times. At the optimal dosage (10 mg/kg), a single dose was as effective as 2 doses. The single administration at all dosages reduced mortality, bacterial shedding, and diarrhea scores and increased body weight gain, compared with findings in untreated pigs (P < 0.01). In this induced infection model, the optimal treatment dosage was determined to be 10 mg/kg administered once.

The effect of ingested epidermal growth factor (EGF) on the small intestinal mucosa of conventionally weaned pigs was determined. At 21 days of age, 39 pigs were randomly distributed into suckling and weaned treatment groups that were administered 124 micrograms of EGF, 372 micrograms of EGF, or the dosing compound daily. Fecal water content was determined daily. On postweaning days 0, 3, 6, and 9, representative pigs from each group were euthanatized, and jejunal mucosa samples were collected for determination of villus-to-crypt ratio, total protein content, disaccharidase activities, and microbiological populations. At postweaning day 3, the 372-micrograms dose of EGF significantly (P less than or equal to 0.05) increased jejunal lactase and sucrase activities in the weaned pigs. Increased lactase activity was not greater than that of the suckling pig controls, whereas sucrase activity was significantly (P less than or equal to 0.05) higher than that of the suckling pig controls. Significant changes were not observed in villus-to-crypt ratio, mucosal protein content, or disaccharidase activities on other collection days.

The efficacy of an ophthalmic ointment containing benzathine cloxacillin for treatment of infectious bovine keratoconjunctivitis was determined in 2 experiments. In the first experiment, Holstein calves (n = 6/group) were inoculated with Moraxella bovis and treated on postinoculation days 3 and 6 with either topically applied benzathine cloxacillin (250 mg/eye) or long-acting oxytetracycline formulation (20 mg/kg of body weight, IM). A third group of inoculated calves remained untreated as controls. For the second experiment, 4 groups of calves (n = 6/group) were inoculated and treated on postinoculation days 3 and 6 with 50, 125, 250, or 375 mg of benzathine cloxacillin; a fifth untreated group served as controls. Ocular specimens were obtained for microbiologic culture, and eyes were observed and assigned a clinical score daily. Eyes were photographed on alternate days. Ulcer surface area was measured, using a planimeter. In experiment 1, the week-2 ulcer surface area measurements for both groups of treated calves were smaller than those for controls. There was a greater frequency of M bovis isolation from the ocular secretions of controls than from those of benzathine cloxacillin-treated calves during postinoculation weeks 2 and 3. The number of M bovis isolations from the benzathine cloxacillin- and oxytetracycline-treated calves was not significantly different at any sample collection interval. On week 3, the scores of the benzathine cloxacillin-treated calves were smaller than those of controls. In experiment 2, calves of the 250- and 375-mg group had smaller scores than did controls. During postinoculation weeks 1 through 3, M bovis was isolated less frequently from the ocular secretions of calves of the 250- and 375-mg groups than from those of the control calves.

The efficacy of paste and granule formulations of pyrantel pamoate against concurrent infections of Toxocara cati and Ancylostoma tubaeforme in cats was examined in a controlled trial. Three groups of 8 cats received either no medication (controls) or pyrantel pamoate in paste or granule formulations at a dosage of 20 mg/kg of body weight. After administration of the paste formulation, fecal egg counts of A tubaeforme and T cati were decreased by 98.6 and 96.4%, respectively, and 100% of hookworms and 93.5% of ascarids were removed from the intestine. After administration of the granule formulation, fecal egg counts of A tubaeforme and T cati were decreased by 99.4 and 78.2%, respectively, and 100% of adult hookworms and 88.9% of ascarids were removed. All reductions of egg counts and worm numbers were significant (P < 0.01). The clinical safety of pyrantel pamoate was evaluated in 4- to 6-week-old kittens. Three groups of 10 kittens received either no medication (controls) or pyrantel pamoate in paste or granule formulations at the rate of 100 mg/kg for 3 consecutive days. Adverse effects were not observed in young kittens following administration of the high dose of pyrantel pamoate.