Objective--To assess efficacy and tolerability of robenacoxib for control of pain and inflammation in dogs undergoing orthopedic surgery. Animals--140 client-owned dogs. Procedures--A multicenter, prospective, randomized, blinded field trial was conducted to compare robenacoxib (97 dogs) and meloxicam (43 dogs). After randomization, each dog received an initial dose (robenacoxib, 2 mg/kg; meloxicam, 0.2 mg/kg) via SC injection before surgery and daily doses (robenacoxib, 1 to 2 mg/kg; meloxicam, 0.1 mg/kg) administered orally for up to 15 days after surgery. Efficacy was assessed by veterinarians and owners via numeric rating scales and visual analogue scales. Safety was assessed on the basis of reported adverse events, clinical signs, results of hematologic and biochemical analyses, and buccal mucosa bleeding times. Results--Treatment groups were balanced with respect to baseline and demographic data. Both treatments provided similar adequate pain control, as assessed with a modified Glasgow pain scale as the primary end point and supported by secondary end points in evaluations conducted by veterinarians and owners. For the primary end point, the ratio of the reciprocal of the scores for robenacoxib to meloxicam was 1.16 (95% confidence interval, 0.98 to 1.37). No dogs required rescue analgesia. Both treatments were associated with only minor adverse events, which were not necessarily related to the administered treatments and did not affect mucosal bleeding times. Conclusions and Clinical Relevance--Robenacoxib provided efficacy and tolerability similar to those of meloxicam for the management of perioperative pain and inflammation in dogs undergoing orthopedic surgery.

Objective—To determine the pharmacokinetic parameters of xylazine, ketamine, and butorphanol (XKB) administered IM and sodium salicylate (SAL) administered PO to calves and to compare drug effects on biomarkers of pain and distress following sham and actual castration and dehorning. Animals—40 Holstein bull calves from 3 farms. Procedures—Calves weighing 108 to 235 kg (n = 10 calves/group) received one of the following treatments prior to sham (period 1) and actual (period 2) castration and dehorning: saline (0.9% NaCl) solution IM (placebo); SAL administered PO through drinking water at concentrations from 2.5 to 5 mg/mL from 24 hours prior to period 1 to 48 hours after period 2; butorphanol (0.025 mg/kg), xylazine (0.05 mg/kg), and ketamine (0.1 mg/kg) coadministered IM immediately prior to both periods; and a combination of SAL and XKB (SAL+XKB). Plasma drug concentrations, average daily gain (ADG), chute exit velocity, serum cortisol concentrations, and electrodermal activity were evaluated. Results—ADG (days 0 to 13) was significantly greater in the SAL and SAL+XKB groups than in the other 2 groups. Calves receiving XKB had reduced chute exit velocity in both periods. Serum cortisol concentrations increased in all groups from period 1 to period 2. However, XKB attenuated the cortisol response for the first hour after castration and dehorning and oral SAL administration reduced the response from 1 to 6 hours. Administration of XKB decreased electrodermal activity scores in both periods. Conclusions and Clinical Relevance—SAL administered PO through drinking water decreased cortisol concentrations and reduced the decrease in ADG associated with castration and dehorning in calves.

Objective—To determine the pharmacokinetics of tramadol and its metabolites O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) in adult horses. Animals—12 mixed-breed horses. Procedures—Horses received tramadol IV (5 mg/kg, over 3 minutes) and orally (10 mg/kg) with a 6-day washout period in a randomized crossover design. Serum samples were collected over 48 hours. Serum tramadol, ODT, and NDT concentrations were measured via high-performance liquid chromatography and analyzed via noncompartmental analysis. Results—Maximum mean ± SEM serum concentrations after IV administration for tramadol, ODT, and NDT were 5,027 ± 638 ng/mL, 0 ng/mL, and 73.7 ± 12.9 ng/mL, respectively. For tramadol, half-life, volume of distribution, area under the curve, and total body clearance after IV administration were 2.55 ± 0.88 hours, 4.02 ± 1.35 L/kg, 2,701 ± 275 h•ng/mL, and 30.1 ± 2.56 mL/min/kg, respectively. Maximal serum concentrations after oral administration for tramadol, ODT, and NDT were 238 ± 41.3 ng/mL, 86.8 ± 17.8 ng/mL, and 159 ± 20.4 ng/mL, respectively. After oral administration, half-life for tramadol, ODT, and NDT was 2.14 ± 0.50 hours, 1.01 ± 0.15 hours, and 2.62 ± 0.49 hours, respectively. Bioavailability of tramadol was 9.50 ± 1.28%. After oral administration, concentrations achieved minimum therapeutic ranges for humans for tramadol (> 100 ng/mL) and ODT (> 10 ng/mL) for 2.2 ± 0.46 hours and 2.04 ± 0.30 hours, respectively. Conclusions and Clinical Relevance—Duration of analgesia after oral administration of tramadol might be < 3 hours in horses, with ODT and the parent compound contributing equally.

Objective—To determine the chemoprophylactic effect of gallium maltolate on the cumulative incidence of pneumonia caused by Rhodococcus equi infection in foals. Animals—483 foals born and raised on 12 equine breeding farms with a history of endemic R equi infections. Procedures—Group 1 foals were treated with a placebo and group 2 foals were treated with gallium maltolate (approx 30 mg/kg, PO, q 24 h) during the first 2 weeks after birth. Foals were monitored for development of pneumonia attributable to R equi infection and for adverse effects of gallium maltolate. Results—There were no significant differences in the cumulative incidence of R equi pneumonia among the 2 groups. Conclusions and Clinical Relevance—Chemoprophylaxis via gallium maltolate administered orally at approximately 30 mg/kg daily for the first 2 weeks after birth failed to reduce the cumulative incidence of pneumonia attributable to R equi infection among foals on breeding farms with endemic R equi infections. Further investigation is needed to identify strategies for control of R equi infections.

Objective: To determine whether therapeutic concentrations of levetiracetam can be achieved in cats and to establish reasonable IV and oral dosing intervals that would not be associated with adverse effects in cats. Animals: 10 healthy purpose-bred cats. Procedures: In a randomized crossover study, levetiracetam (20 mg/kg) was administered orally and IV to each cat. Blood samples were collected 0, 10, 20, and 40 minutes and 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours after administration. Plasma levetiracetam concentrations were determined via high-performance liquid chromatography. Results: Mean ± SD peak concentration was 25.54 ± 7.97 μg/mL. The mean y-intercept for IV administration was 37.52 ± 6.79 μg/mL. Half-life (harmonic mean ± pseudo-SD) was 2.95 ± 0.95 hours and 2.86 ± 0.65 hours for oral and IV administration, respectively. Mean volume of distribution at steady state was 0.52 ± 0.09 L/kg, and mean clearance was 2.0 ± 0.60 mL/kg/min. Mean oral bioavailability was 102 ± 39%. Plasma drug concentrations were maintained in the therapeutic range reported for humans (5 to 45 μg/mL) for at least 9 hours after administration in 7 of 10 cats. Only mild, transient hypersalivation was evident in some cats after oral administration. Conclusions and Clinical Relevance: Levetiracetam (20 mg/kg) administered orally or IV to cats every 8 hours should achieve and maintain concentrations within the therapeutic range for humans. Levetiracetam administration has favorable pharmacokinetics for clinical use, was apparently tolerated well, and may be a reasonable alternative antiepileptic drug in cats.

Objective--To develop a simple extractionless method for detection of rosiglitazone in canine plasma and test the method in a pharmacokinetic study after oral administration of rosiglitazone in dogs. Animals--3 client-owned dogs with cancer. Procedures--High-performance liquid chromatography-tandem mass spectrometry was performed on canine plasma. The 3 dogs with cancer in the pharmacokinetic study were assessed via physical examination and clinicopathologic evaluation and considered otherwise healthy. Food was withheld for 12 hours, and dogs were administered a single dose (4 mg/m2) of rosiglitazone. Plasma was collected at various times, processed, and analyzed for rosiglitazone. Results--The developed method was robust and detected a minimum of 0.3 ng of rosiglitazone/mL. Mean ± SD maximum plasma concentration was 205.2 ± 79.1 ng/mL, which occurred at 3 ± 1 hours, and mean ± SD elimination half-life was 1.4 ± 0.4 hours. The area under the plasma rosiglitazone concentration-versus-time curve varied widely among the 3 dogs (mean ± SD, 652.2 ± 351.3 ng/h/mL). Conclusions and Clinical Relevance--A simple extractionless method for detection of rosiglitazone in canine plasma was developed and was validated with excellent sensitivity, accuracy, precision, and recovery. The method enabled unambiguous evaluation and quantitation of rosiglitazone in canine plasma. This method will be useful for pharmacokinetic, bioavailability, or drug-drug interaction studies. Oral rosiglitazone administration was well tolerated in the dogs.

Objective—To investigate the effects of twice-daily oral administration of hydrocortisone on the bile acids composition of gallbladder bile in dogs. Animals—6 placebo-treated control dogs and 6 hydrocortisone-treated dogs. Procedures—Dogs received hydrocortisone (median dose, 8.5 mg/kg) or a gelatin capsule (control group) orally every 12 hours for 84 days. Gallbladder bile samples were obtained via percutaneous ultrasound-guided cholecystocentesis from each dog before (day 0 [baseline]), during (days 28, 56, and 84), and after (days 28p, 56p, and 84p) treatment for differentiated quantification of unconjugated bile acids and taurine-conjugated and glycine-conjugated bile acids via high-performance liquid chromatography–tandem mass spectrometry. Results—Treatment with hydrocortisone for 84 days resulted in significant and reversible increases in the concentrations of unconjugated bile acids (ie, cholic, chenodeoxycholic, and deoxycholic acids) and a significant and reversible decrease in the concentration of total taurine-conjugated bile acids, compared with baseline or control group values. Treatment with hydrocortisone had no effect on bile concentrations of glycine-conjugated bile acids. Conclusions and Clinical Relevance—In dogs, hydrocortisone administration caused reversible shifts toward higher concentrations of the more hydrophobic unconjugated bile acids (chenodeoxycholic acid and deoxycholic acid) and toward lower concentrations of the amphipathic taurine-conjugated bile acids in gallbladder bile. These data suggest that similar bile acids changes could cause major alterations in gallbladder structure or function over time in hypercortisolemic dogs.

Objective—To determine whether oral administration of metoclopramide or a commercially available powdered whole grapefruit (PWG) nutraceutical in combination with cyclosporine enhances systemic availability of cyclosporine in dogs. Sample—8 healthy mixed-breed dogs in part 1 and 6 of these 8 dogs in part 2. Procedures—Cyclosporine pharmacokinetics were determined over the course of 24 hours after oral administration of cyclosporine (5 mg/kg) alone, cyclosporine with metoclopramide (0.3 to 0.5 mg/kg), cyclosporine with 2 g of PWG, or cyclosporine combined with both metoclopramide and 2 g of PWG by use of a Latin square crossover study with a 14-day washout period between treatments. Sixty days later, 6 of the 8 dogs were given 10 g of PWG followed by cyclosporine, and pharmacokinetic parameters were compared with those previously obtained after administration of cyclosporine alone. Results—Although metoclopramide or coadministration of metoclopramide and 2 g of PWG had no effect on the pharmacokinetic parameters of cyclosporine, compared with results for cyclosporine alone, the higher (10-g) dose of PWG resulted in 29% faster mean time to maximal plasma cyclosporine concentration, 54% larger area under the curve, and 38% lower apparent oral clearance. Conclusions and Clinical Relevance—Adjustment of the cyclosporine dose may not be needed when metoclopramide is coadministered orally to prevent common adverse effects of cyclosporine. Powdered whole grapefruit has the potential to reduce the required orally administered dose of cyclosporine but only when PWG is used in an amount (at least 10 g) that is currently not cost-effective.

Objective-To determine the effects of once-daily oral administration of N-acetyl-d-glucosamine (NAG) on plasma and urine glycosaminoglycan (GAG) concentrations in cats with idiopathic cystitis (IC). Animals-19 cats with IC and 10 clinically normal cats. Procedures-Cats with IC were randomly assigned to receive 250 mg of NAG in capsule form orally once daily for 28 days (n = 12) or a placebo (capsule containing cellulose) orally once daily for the same period (7). In cats with IC, plasma and urine GAG concentrations and urine creatinine concentration were measured on days 0 (immediately before first dose), 7, 14, 21, 28, and 56. For purposes of comparison, those variables were measured in 10 clinically normal cats on day 0. Results-Mean +/- SEM urine GAG-to-creatinine concentration ratios (day 0 data) for cats with IC and clinically normal cats differed significantly (3.11 +/- 0.62 μg/mL and 14.23 +/- 3.47 μg/mL, respectively). For cats with IC, mean plasma GAG concentration in NAG-treated cats (39.96 +/- 5.34 micrograms/mL) was higher than that in placebo-treated cats (24.20 +/- 3.35 micrograms/mL) on day 21. In the NAG-treated cats, plasma GAG concentration on days 21 (39.96 +/- 5.34 micrograms/mL) and 28 (39.91 +/- 6.74 micrograms/mL) differed significantly from the day 0 concentration (27.46 +/- 3.90 micrograms/mL). Conclusions and Clinical Relevance-Cats with IC have lower urinary GAG-to-creatinine concentration ratios than did clinically normal cats. Administration of NAG (250 mg, PO, q 24 h) significantly increased plasma GAG concentrations in cats with IC after 21 days of treatment.