Prednisone was given orally to 12 dogs daily for 35 days at an anti-inflammatory dosage (1.1 mg/kg of body weight in divided dose, q 12 h) to study its effect on thyroxine (T4) and triiodothyronine (T3) metabolism. Six of these dogs were surgically thyroidectomized (THX-Pred) and maintained in euthyroid status by daily SC injections of T4 to study peripheral metabolism while receiving prednisone; 6 dogs with intact thyroid gland (Pred) were given prednisone; and 6 additional dogs were given gelatin capsule vehicle as a control group (Ctrl). Baseline T4 concentration after 4 weeks of treatment was not significantly different in dogs of the THX-Pred or Pred group (mean +/- SEM, 2.58 +/- 0.28 or 3.38 +/- 0.58 microgram/dl, respectively) vs dogs of the Ctrl group (2.12 +/- 0.30 microgram/dl). A supranormal response of T4 to thyrotropin was observed in dogs of the Pred group, but the T4 response to thyrotropin-releasing hormone was normal. Baseline T3 concentration in dogs of both steroid-treated groups was significantly (P < 0.05) lower after 2 and 4 weeks of prednisone administration vs pretreatment values, but normalized 2 weeks after prednisone was stopped. Free T3 (FT3) and T4 (FT4) fractions and absolute FT3 and FT, concentrations were not altered by prednisone administration. Reverse T3 (rT3) concentration in vehicle-treated Ctrl dogs (26.6 +/- 3.5 ng/dl) was not different from rT3 concentration in dogs of the THX-Pred (25.7 +/- 4.3 ng/dl) and Pred (28.9 +/- 3.8 ng/dl) groups after 4 weeks of medication. These data indicate that daily oral administration of such anti-inflammatory dose of prednisone for 1 month reduces baseline serum T3 concentration, does not alter serum T4 concentration, and enhances thyroidal sensitivity to thyrotropin.

Intestinal permeability was assessed in 12 healthy cats by use of a differential sugar absorption test. A 50-ml isotonic aqueous solution containing a combination of 1.8 g of the disaccharide lactulose and 1.7 g of the monosaccharide mannitol was administered to cats via nasogastric tube. Urine was collected after 6 hours, and all urine samples were analyzed the same day, using a gas-liquid chromatographic technique (GLC) and an enzymatic assay (ENZ). Median urinary recovery of lactulose was 0.27 and 0.54% determined by GLC and ENZ, respectively. Differences between these groups were statistically significant (P = 0.023), and correlation between assays was high (r = 0.94, P < 0.01). Median urinary recovery of mannitol was 1.93 and 2.09% for GLC and ENZ, respectively. There were no statistically significant differences between these groups and the correlation between assays was high (r = 0.85, P < 0.01). The median lactulose-to-mannitol ratio was 0.29, using GLC, and was 0.52, using ENZ. Correlation of these ratios was again high (r = 0.93, P < 0.01).

Four-week-old chickens were inoculated orally with 1,000 or 100,000 oocysts of the ME-49 or GT-1 strain of Toxoplasma gondii, and their antibody responses were measured, using the direct modified agglutination test, latex agglutination test, indirect hemagglutination test, ELISA, and the Sabin-Feldman dye test. Antibodies against T gondii were detected by use of the modified agglutination test and ELISA within 2 weeks of oocyst inoculation, and antibodies persisted until termination of the study by postinoculation day 68. The latex agglutination test was insensitive in detecting T gondii antibodies, and antibodies were not detected by use of the dye and indirect hemagglutination tests. Of tissues bioassayed in mice for tissue cysts by pepsin digestion of individual organs of chickens on postinoculation day 68, tissue cysts were found in the brain of all 5, heart of 3, and leg muscles of 2, but not in the liver and breast muscles. None of the birds developed clinical toxoplasmosis.

Five healthy adult mares and 1 gelding were given a single dose (15 mg/kg of body weight) of metronidazole per rectum. After manual evacuation of feces from the rectum, a suspension of crushed tablets and water (40 ml) was administered via a 28-F catheter advanced 30 cm into the rectum. Blood samples were obtained by jugular venipuncture, and metronidazole concentration was measured serially for the 14 hours after drug administration. Mean serum concentration of metronidazole peaked at 4.5 micrograms/ml, 0.83 hour after administration, and decreased to 0.38 micrograms/ml, 14 hours after administration. Mean elimination rate constant was 0.23/h, and the harmonic mean elimination half-life was 3.04 hours. Further study is necessary to determine a therapeutic dose regimen for metronidazole administered per rectum.

Twelve healthy dogs were used to determine the cardiorespiratory effects of IV administered ketamine (10 mg/kg of body weight) and midazolam (0.5 mg/ kg). Half the dogs received a ketamine-midazolam combination (K-M) as a bolus over 30 seconds and the other half received the K-M as an infusion over 15 minutes. Induction of anesthesia by use of K-M was good in all dogs. Ketamine-midazolam combination as a bolus or infusion induced minimal cardiorespiratory effects, except for significant (p < 0.05) increases in mean heart rate and rate-pressure product. The increase in heart rate was greater in dogs of the infusion group. Mild and transient respiratory depression was observed in dogs of both groups immediately after administration of K-M, but was greater in dogs of the bolus group than in dogs of the infusion group. Duration of action of K-M for chemical restraint was short. Salivation and defecation were observed in a few dogs. Extreme muscular tone developed in 1 dog after K-M bolus administration.

Twelve mature (5 sexually intact males, 4 castrated males, and 3 females) mixed-breed dogs were surgically thyroidectomized and used in a Latin-square design pharmacokinetic study of orally administered L-thyroxine. The dogs were treated with 44, 22, and 11 Kg of L-thyroxine/kg as a single morning dose or in divided doses, morning and evening. Serum concentration of thyroxine (T4) was evaluated to determine a number of pharmacokinetic variables for comparison. Mean steady-state concentrations (C(SS)) were determined from the area under the curve. Variables were analyzed for comparisons between dosages by use of ANOVA. Concentration at steady state was highest for dogs of the 44-micrograms/kg of body weight once-daily group and was lowest for dogs of the group given 11 micrograms/kg in 2 daily doses. Single daily administration resulted in higher C(SS), except at the 22-micrograms/kg/d dosage. Clearance was faster for the 22- and 44-micrograms/kg/d dosages than for the 11-micrograms/kg/d dosage. The half-life (t(1/2)) and mean residence time (MRT) also were shorter for the 44-micrograms/kg/d dosage, possibly indicating more rapid elimination of the drug at higher doses and dose-dependent kinetics. Perhaps, as the dogs' metabolism increased with higher iodothyronine concentrations, hormone degradation was accelerated. Interval (divided vs single dose) caused some expected changes: maximal concentration was higher and minimal concentration was lower when single administration was used. These undulations resulted in iodothyronine concentrations above the physiologic range for a number of hours, whereas concentration closer to physiologic ranges was achieved by use of divided doses. Delayed absorption (lag time) was seen in 37 of the 72 data sets, but was generally short, about 0.25 hour. Mean time to maximal concentration was 3 to 4 hours. At the higher dosages, serum total T4 concentration was high normal or above normal during most of the time after L-thyroxine administration, but serum concentration of total 3,5,3'-triiodothyronine did not remain within the normal range until the 44-micrograms/kg/d dosage was used. The customary dosage of 22 micrograms/kg/d (0.1 mg/10 lb/d) may not be adequate for most dogs. Pharmacokinetic variables appear to be highly dependent on the individual dog. Those with rapid absorption and higher concentration tended to have these characteristics at each dosage in this study. The pharmacokinetic variables, therefore, appear to be highly individualized, and dosages recommended for treatment of hypothyroidism should be considered to be only a starting point for the average dog. To avoid underdosing or overdosing, monitoring of treatment to adjust dose for individual dog kinetic variables seems to be imperative.

Prednisone was administered orally for 4 weeks at a dosage of 1.1 mg/kg of body weight/d, in divided dose every 12 hours, to a group of healthy adult dogs (n = 12). Intravenous glucose tolerance testing was performed before and after the 28-day regimen in each dog, as well as in dogs of a control group (n = 6). Glucose metabolism was evaluated by measurement of preprandial plasma insulin and glucose concentrations, total insulin secretion, and fractional clearance of glucose. Mean preprandial plasma insulin and glucose concentrations were not increased after the 4-week regimen of prednisone. Total insulin secretion in response to an IV administered glucose load was not increased in treated dogs, compared with pretreatment values or with values for control dogs. The fractional clearance of glucose was also not altered in dogs given prednisone. Results indicate that anti-inflammatory doses of prednisone, given orally for 4 weeks, probably do not alter insulin sensitivity or glucose tolerance in clinically normal dogs.

Albendazole, administered orally at a dose rate of 25 mg/kg of body weight to presumed pregnant cows or heifers on days 21, 31, 41, 51, and 61 of gestation, did not induce toxicosis in embryos or fetuses, and all calves born were structurally normal. Albendazole administration at a rate of 25 mg/kg to cows at 7 and/or 14 days of gestation decreased the apparent conception rate (ie, embryolethality), but did not have a teratogenic effect. Apparent embryolethality was greater in cows administered 25 mg/ kg only on day 14, compared with those administered the drug only on day 7. Single dosage of 25 mg/kg given in the final 3 months of gestation did not induce abortion. There were no adverse effects of albendazole at a dosage of 10 or 15 mg/kg on developing embryos or fetuses when administered to presumed pregnant cows at various times in early gestation.

Topically applied demecarium bromide (0.125 and 0.25%) and echothiophate iodide (0.125 and 0.25%) solutions were evaluated in Beagles with normotensive eyes and Beagles with inherited glaucoma. In single-dose studies, the effects of intraocular pressure (IOP) and pupil size (PS) were measured in eyes before drug treatment and in drug- and nondrug-treated eyes. Both concentrations of the 2 drugs induced long-term miosis and decrease in IOP in normotensive eyes of Beagles and of eyes of Beagles with inherited glaucoma. Demecarium bromide (0.125 and 0.5%) decreased IOP for 49 and 55 hours, respectively. Echothiophate iodide (0.125 and 0.5%) reduced IOP for 25 and 53 hours, respectively. The miosis associated with both concentrations of the 2 drugs generally paralleled the decreases in IOP.

Pharmacokinetic variables of ibuprofen were studied in 6 adult lactating dairy goats after single administration of the drug (14 and 25 mg/kg of body weight, IV, and 50 and 100 mg/kg, PO). Each of the goats was given all doses, with a minimum of 1 week between doses. Ibuprofen concentration in serum was analyzed by use of high-performance liquid chromatography. The lower limit of detection for the ibuprofen assay was 50 ng/ml. Ibuprofen pharmacokinetic variables after IV administration best fit an open two-compartment model. Geometric mean (range) volume of distribution at steady state was 0.16 (0.11 to 0.19) and 0.17 (0.15 to 0.19) lag, and terminal half-life was 1.08 (0.79 to 1.70) and 1.27 (1.03 to 1.88) hours, for ibuprofen dosages of 14 and 25 mg/kg, respectively. After 50 and 100 mg/kg administered orally, bioavailability was 90.8 and 106%, respectively. Area under the curve increased linearly with dose administered. Adverse effects were not observed in goats given ibuprofen.