OBJECTIVE To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses. ANIMALS 4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments. PROCEDURES 12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and prostaglandin E metabolites) served as indicators of COX activity, and serum drug concentrations were measured by use of high-performance liquid chromatography. An in vitro coagulation-induced thromboxane B2 assay was used to calculate drug concentration-COX-1 inhibition curves. Effect of time and treatment on COX activity was determined. Agreement between in vitro and ex vivo measurement of COX activity was assessed with Bland-Altman analysis. RESULTS At 2 and 24 hours after NSAID administration, COX-1 activity was reduced, compared with baseline activity, for the flunixin meglumine group only and relative COX-1 activity was significantly greater for the firocoxib group, compared with that for the flunixin meglumine group. There was no significant change in COX-2 activity after surgery for either group. Bland-Altman analysis revealed poor agreement between in vitro and ex vivo measurement of COX-1 activity. CONCLUSIONS AND CLINICAL RELEVANCE Compared with flunixin meglumine, firocoxib had COX-1-sparing effects ex vivo in equine patients that underwent elective surgery.

OBJECTIVE To investigate the anti-inflammatory and immunomodulatory properties of tulathromycin in vitro and in experimental models of Actinobacillus pleuropneumoniae–induced pleuropneumonia and zymosan-induced pulmonary inflammation in pigs. ANIMALS Blood samples from six 8- to 30-week-old healthy male pigs for the in vitro experiment and sixty-five 3-week-old specific pathogen–free pigs. PROCEDURES Neutrophils and monocyte-derived macrophages were isolated from blood samples. Isolated cells were exposed to tulathromycin (0.02 to 2.0 mg/mL) for various durations and assessed for markers of apoptosis and efferocytosis. For in vivo experiments, pigs were inoculated intratracheally with A pleuropneumoniae, zymosan, or PBS solution (control group) with or without tulathromycin pretreatment (2.5 mg/kg, IM). Bronchoalveolar lavage fluid was collected 3 and 24 hours after inoculation and analyzed for proinflammatory mediators, leukocyte apoptosis, and efferocytosis. RESULTS In vitro, tulathromycin induced time- and concentration-dependent apoptosis in neutrophils, which enhanced their subsequent clearance by macrophages. In the lungs of both A leuropneumoniae– and zymosan-challenged pigs, tulathromycin promoted leukocyte apoptosis and efferocytosis and inhibited proinflammatory leukotriene B4 production, with a concurrent reduction in leukocyte necrosis relative to that of control pigs. Tulathromycin also attenuated the degree of lung damage and lesion progression in A pleuropneumoniae–inoculated pigs. CONCLUSIONS AND CLINICAL RELEVANCE Tulathromycin had immunomodulatory effects in leukocytes in vitro and anti-inflammatory effects in pigs in experimental models of A pleuropneumoniae infection and nonmicrobial-induced pulmonary inflammation. These data suggested that in addition to its antimicrobial properties, tulathromycin may dampen severe proinflammatory responses and drive resolution of inflammation in pigs with microbial pulmonary infections.

OBJECTIVE To assess the urinary protein-to-creatinine ratio (UPCR) of healthy sexually intact male dogs and to compare the UPCR of these dogs before and after castration. ANIMALS 19 client- or shelter-owned healthy adult sexually intact male dogs. PROCEDURES Physical, hematologic, and biochemical examinations and urinalysis (including calculation of the UPCR) were performed on each dog. Dogs were then castrated, and physical examination and urinalysis (including calculation of the UPCR) were performed again at least 15 days after castration. RESULTS A dipstick test yielded positive results for protein in the urine of 10 sexually intact male dogs, but the UPCR was < 0.5 for all sexually intact male dogs. Mean UPCR for sexually intact male dogs was 0.12 (range, 0.10 to 0.32). The UPCR was < 0.2 for all castrated dogs, except for 1. Mean UPCR for all castrated dogs was 0.08 (range, 0.05 to 0.69). There was a significant difference between mean UPCR before and after castration. CONCLUSIONS AND CLINICAL RELEVANCE In this study, pathological proteinuria was not detected in sexually intact male dogs. Positive results for a urine dipstick test should be interpreted with caution in sexually intact male dogs and should be confirmed by assessment of the UPCR. An increased UPCR in sexually intact male dogs may be considered abnormal.

OBJECTIVE To determine pharmacokinetics of butorphanol delivered via osmotic pumps in common peafowl (Pavo cristatus) as a method for analgesic administration to avian species. ANIMALS 14 healthy adult male common peafowl. PROCEDURES A preliminary experiment was conducted with 2 birds to establish time point and concentration requirements. Then, the remaining 12 birds were anesthetized, and 2 osmotic pumps containing butorphanol (volume, 2 mL; mean dosage, 247 μg/kg/h) were implanted subcutaneously in each bird for 7 days prior to removal. Blood samples were collected before pump implantation (time 0); 3, 6, 12, 24, 48, 72, 96, 120, 144, and 168 hours after pump implantation; and 3 and 6 hours after pump removal. Plasma butorphanol concentrations were measured via liquid chromatography–mass spectrometry. RESULTS Plasma concentrations peaked (mean, 106.4 μg/L; range, 61.8 to 133.0 μg/L) at a mean of 39.0 hours, with no evidence of sedation in any bird. After pump removal, butorphanol was rapidly eliminated (half-life, 1.45 hours; range, 1.31 to 1.64 hours; n = 5). Mean clearance per fraction of dose absorbed was 2.89 L/kg/h (range, 2.00 to 5.55 L/kg/h). Mean amount of time the plasma butorphanol concentration was ≥ 60 μg/L was 85.6 hours (range, 3.5 to 155.3 hours). CONCLUSIONS AND CLINICAL RELEVANCE Plasma concentrations of butorphanol in common peafowl were maintained at or above reported efficacious analgesic concentrations. This study established a method for administering analgesics to avian patients without the need for frequent handling or injections. Use of these osmotic pumps may provide options for avian analgesia.

OBJECTIVE To evaluate pharmacokinetics of ammonium tetrathiomolybdate (TTM) after IV and oral administration to dogs and effects of TTM administration on trace mineral concentrations. ANIMALS 8 adult Beagles and Beagle crossbreds (4 sexually intact males and 4 sexually intact females). PROCEDURES Dogs received TTM (1 mg/kg) IV and orally in a randomized crossover study. Serum molybdenum and copper concentrations were measured via inductively coupled plasma mass spectrometry in samples obtained 0 to 72 hours after administration. Pharmacokinetics was determined via noncompartmental analysis. RESULTS For IV administration, mean ± SD terminal elimination rate constant, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 4.9 ± 0.6 μg/mL, 30.7 ± 5.4 μg/mL•h, and 27.7 ± 6.8 hours, respectively. For oral administration, mean ± SD terminal elimination rate constant, time to maximum concentration, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 3.0 ± 3.5 hours, 0.2 ± 0.4 μg/mL, 6.5 ± 8.0 μg/mL•h, and 26.8 ± 8.0 hours, respectively. Oral bioavailability was 21 ± 22%. Serum copper concentrations increased significantly after IV and oral administration. Emesis occurred after IV (2 dogs) and oral administration (3 dogs). CONCLUSIONS AND CLINICAL RELEVANCE Pharmacokinetics for TTM after a single IV and oral administration was determined for clinically normal dogs. Absorption of TTM after oral administration was variable. Increased serum copper concentrations suggested that TTM mobilized tissue copper. Further studies will be needed to evaluate the potential therapeutic use of TTM in copper-associated chronic hepatitis of dogs.

OBJECTIVE To assess changes in biochemical and biophysical properties of canine RBCs during cold (1° to 6°C) storage in a licensed RBC additive solution (the RBC preservation solution designated AS-1) supplemented with ascorbic acid. SAMPLE Blood samples from 7 neutered male Greyhounds; all dogs had negative results when tested for dog erythrocyte antigen 1.1. PROCEDURES Blood was collected into citrate-phosphate-dextrose and stored in AS-1. Stored RBCs were supplemented with 7.1mM ascorbic acid or with saline (0.9% NaCl) solution (control samples). Several biochemical and biophysical properties of RBCs were measured, including percentage hemolysis, oxygen-hemoglobin equilibrium, and the kinetic rate constants for O2 dissociation, carbon monoxide association, and nitric oxide dioxygenation. RESULTS Greyhound RBCs stored in AS-1 supplemented with ascorbic acid did not have significantly decreased hemolysis, compared with results for the control samples, during the storage period. CONCLUSIONS AND CLINICAL RELEVANCE In this study, ascorbic acid did not reduce hemolysis during storage. Several changes in stored canine RBCs were identified as part of the hypothermic storage lesion.

OBJECTIVE To determine the minimum infusion rate (MIR) of propofol required to prevent movement in response to a noxious stimulus in dogs anesthetized with propofol alone or propofol in combination with a constant rate infusion (CRI) of ketamine. ANIMALS 6 male Beagles. PROCEDURES Dogs were anesthetized on 3 occasions, at weekly intervals, with propofol alone (loading dose, 6 mg/kg; initial CRI, 0.45 mg/kg/min), propofol (loading dose, 5 mg/kg; initial CRI, 0.35 mg/kg/min) and a low dose of ketamine (loading dose, 2 mg/kg; CRI, 0.025 mg/kg/min), or propofol (loading dose, 4 mg/kg; initial CRI, 0.3 mg/kg/min) and a high dose of ketamine (loading dose, 3 mg/kg; CRI, 0.05 mg/kg/min). After 60 minutes, the propofol MIR required to prevent movement in response to a noxious electrical stimulus was determined in duplicate. RESULTS Least squares mean ± SEM propofol MIRs required to prevent movement in response to the noxious stimulus were 0.76 ± 0.1 mg/kg/min, 0.60 ± 0.1 mg/kg/min, and 0.41 ± 0.1 mg/kg/min when dogs were anesthetized with propofol alone, propofol and low-dose ketamine, and propofol and high-dose ketamine, respectively. There were significant decreases in the propofol MIR required to prevent movement in response to the noxious stimulus when dogs were anesthetized with propofol and low-dose ketamine (27 ± 10%) or with propofol and high-dose ketamine (30 ± 10%). CONCLUSIONS AND CLINICAL RELEVANCE Ketamine, at the doses studied, significantly decreased the propofol MIR required to prevent movement in response to a noxious stimulus in dogs.