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 characterize the relationship between plasma dexmedetomidine concentration and the temperature difference between the thermal threshold and skin temperature (ΔT) and between plasma dexmedetomidine concentration and sedation score in healthy cats. Animals-5 healthy adult spayed female cats. Procedures-Cats received IV administrations of saline (0.9% NaCl) solution, dexmedetomidine (5, 20, or 50 μg/kg), or acepromazine (0.1 mg/kg). Blood samples were collected and thermal threshold and sedation score were determined before and at various times up to 8 hours after drug administration. In addition, cats received an IV infusion of dexmedetomidine that targeted a concentration achieving 99% of the maximum effect on ΔT. Results-No change in ΔT over time was found for the saline solution and acepromazine treatments; ΔT increased for 45 minutes when cats received dexmedetomidine at 5 and 20 μg/kg and for 180 minutes when cats received dexmedetomidine at 50 μg/kg. No change in sedation score over time was found for saline solution. Sedation score increased for 120 minutes after cats received acepromazine and for 60, 120, and 180 minutes after cats received dexmedetomidine at 5, 20, and 50 μg/kg, respectively. The plasma dexmedetomidine concentration–effect relationships for the effect on ΔT and sedation score were almost identical. The plasma dexmedetomidine concentration after infusion was lower than targeted, and ΔT was not significantly affected. Conclusions and Clinical Relevance-Dexmedetomidine administration to cats resulted in thermal analgesia and also profound sedation. These data may be useful for predicting the course of thermal analgesia and sedation after dexmedetomidine administration to cats.

Objective-To evaluate antinociceptive effects and pharmacokinetics of butorphanol tartrate after IM administration to American kestrels (Falco sparverius). Animals-Fifteen 2- to 3-year-old American kestrels (6 males and 9 females). Procedures-Butorphanol (1, 3, and 6 mg/kg) and saline (0.9% NaCl) solution were administered IM to birds in a crossover experimental design. Agitation-sedation scores and foot withdrawal response to a thermal stimulus were determined 30 to 60 minutes before (baseline) and 0.5, 1.5, 3, and 6 hours after treatment. For the pharmacokinetic analysis, butorphanol (6 mg/kg, IM) was administered in the pectoral muscles of each of 12 birds. Results-In male kestrels, butorphanol did not significantly increase thermal thresholds for foot withdrawal, compared with results for saline solution administration. However, at 1.5 hours after administration of 6 mg of butorphanol/kg, the thermal threshold was significantly decreased, compared with the baseline value. Foot withdrawal threshold for female kestrels after butorphanol administration did not differ significantly from that after saline solution administration. However, compared with the baseline value, withdrawal threshold was significantly increased for 1 mg/kg at 0.5 and 6 hours, 3 mg/kg at 6 hours, and 6 mg/kg at 3 hours. There were no significant differences in mean sedation-agitation scores, except for males at 1.5 hours after administration of 6 mg/kg. Conclusion and Clinical Relevance-Butorphanol did not cause thermal antinociception suggestive of analgesia in American kestrels. Sex-dependent responses were identified. Further studies are needed to evaluate the analgesic effects of butorphanol in raptors.

Objective-To determine the pharmacokinetics of ceftiofur crystalline-free acid (CCFA) following SC administration of a single dose to sheep. Animals-9 healthy adult female Suffolk-crossbred sheep. Procedures-Each sheep was administered 6.6 mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were collected at predetermined intervals for 14 days. Serum concentration of ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid chromatography. Pharmacokinetic parameters were determined by compartmental and noncompartmental methods. Results-Pharmacokinetics for CCFA following SC administration in sheep was best described with a 1-compartment model. Mean +/- SD area under the concentration-time curve from time 0 to infinity, peak serum concentration, and time to peak serum concentration were 206.6 +/- 24.8 μ•h/mL, 2.4 +/- 0.5 μg/mL, and 23.1 +/- 10.1 h, respectively. Serum CFAE concentrations ≥ 1 μg/mL (the target serum CFAE concentration for treatment of disease caused by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to 4.9 days. No significant adverse reactions to CCFA administration were observed. Conclusions and Clinical Relevance-Results indicated that adequate therapeutic serum concentrations of CFAE for treatment of disease caused by M haemolytica and P multocida were achieved in sheep following SC administration of a single dose (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common respiratory tract pathogens in sheep.

Objective—To determine the pharmacokinetics of cefovecin sodium after SC administration to Hermann's tortoises (Testudo hermanni). Animals—23 healthy adult Hermann's tortoises (15 males and 8 females). Procedures—Cefovecin (8.0 mg/kg) was injected once in the subcutis of the neck region of Hermann's tortoises, and blood samples were obtained at predetermined time points. Plasma cefovecin concentrations were measured via ultraperformance liquid chromatography coupled to tandem mass spectrometry, and pharmacokinetic parameters were calculated with a noncompartmental model. Plasma protein concentration was quantified, and the percentage of cefovecin bound to protein was estimated with a centrifugation technique. Results—Cefovecin was absorbed rapidly, reaching maximum plasma concentrations between 35 minutes and 2 hours after administration, with the exception of 1 group, in which it was reached after 4 hours. The mean ± SD time to maximum concentration was 1.22 ± 1.14 hours; area under the concentration-time curve was 220.35 ± 36.18 h•μg/mL The mean protein-bound fraction of cefovecin ranged from 41.3% to 47.5%. No adverse effects were observed. Conclusions and Clinical Relevance—Administration of a single dose of cefovecin SC appeared to be well-tolerated in this population of tortoises. Results of pharmacokinetic analysis indicated that the 2-week dosing interval suggested for dogs and cats cannot be considered effective in tortoises; however, further research is needed to determine therapeutic concentrations of the drug and appropriate dose ranges.

Objective-To evaluate the effects of a single incremental exercise test (IET) on mRNA expression and protein content of monocarboxylate transporter (MCT) 1 and MCT4 in the gluteus medius muscle of Thoroughbreds. Animals-12 Thoroughbreds (6 males and 6 females; age, 3 to 4 years). Procedures-Horses underwent an IET before and after 18 weeks of high-intensity exercise training (HIT). Horses were exercised at 90% of maximal oxygen consumption for 3 minutes during the initial 10 weeks of HIT and 110% of maximal oxygen consumption for 3 minutes during the last 8 weeks of HIT. Gluteus medius muscle biopsy specimens were obtained from horses before (baseline), immediately after, and at 3, 6, and 24 hours after the IET. Results-Expression of MCT1 and MCT4 mRNA was upregulated at 3 and 6 hours after the IET in muscle specimens obtained from horses prior to HIT (untrained horses) and at 6 hours after the IET in muscle specimens obtained from horses after HIT (trained horses). For both untrained and trained horses, MCT1 and MCT4 protein contents were increased at 6 hours after the IET and did not differ at 24 hours after the IET, compared with those at baseline. Conclusions and Clinical Relevance-Results indicated that a single IET resulted in transient increases in MCT1 and MCT4 mRNA expression and protein content in untrained and trained horses. These results may be important for the elucidation of exercise-induced alterations in lactate metabolism.

Objective: To develop a technique for radiographic evaluation of the gastrointestinal tract in ball pythons (Python regius). Samples: 10 ball python cadavers (5 males and 5 females) and 18 healthy adult ball pythons (10 males and 8 females). Procedures: Live snakes were allocated to 3 groups (A, B, and C). A dose (25 mL/kg) of barium sulfate suspension at 3 concentrations (25%, 35%, and 45% [wt/vol]) was administered through an esophageal probe to snakes in groups A, B, and C, respectively. Each evaluation ended when all the contrast medium had reached the large intestine. Transit times through the esophagus, stomach, and small intestine were recorded. Imaging quality was evaluated by 3 investigators who assigned a grading score on the basis of predetermined criteria. Statistical analysis was conducted to evaluate differences in quality among the study groups. Results: The esophagus and stomach had a consistent distribution pattern of contrast medium, whereas 3 distribution patterns of contrast medium were identified in the small intestine, regardless of barium concentration. Significant differences in imaging quality were detected among the 3 groups. Conclusions and Clinical Relevance: Radiographic procedures were tolerated well by all snakes. The 35% concentration of contrast medium yielded the best imaging quality. Use of contrast medium for evaluation of the cranial portion of the gastrointestinal tract could be a reliable technique for the diagnosis of gastrointestinal diseases in ball pythons. However, results of this study may not translate to other snake species because of variables identified in this group of snakes.

Objective: To determine the impact of a free-choice diet on nutritional intake and body condition of feral horses. Animals: Cadavers of 41 feral horses from 5 Australian locations. Procedures: Body condition score (BCS) was determined (scale of 1 to 9), and the stomach was removed from horses during postmortem examination. Stomach contents were analyzed for nutritional variables and macroelement and microelement concentrations. Data were compared among the locations and also compared with recommended daily intakes for horses. Results: Mean BCS varied by location; all horses were judged to be moderately thin. The BCS for males was 1 to 3 points higher than that of females. Amount of protein in the stomach contents varied from 4.3% to 14.9% and was significantly associated with BCS. Amounts of water-soluble carbohydrate and ethanol-soluble carbohydrate in stomach contents of feral horses from all 5 locations were higher than those expected for horses eating high-quality forage. Some macroelement and microelement concentrations were grossly excessive, whereas others were grossly deficient. There was no evidence of ill health among the horses. Conclusions and Clinical Relevance: Results suggested that the diet for several populations of feral horses in Australia appeared less than optimal. However, neither low BCS nor trace mineral deficiency appeared to affect survival of the horses. Additional studies on food sources in these regions, including analysis of water-soluble carbohydrate, ethanol-soluble carbohydrate, and mineral concentrations, are warranted to determine the provenance of such rich sources of nutrients. Determination of the optimal diet for horses may need revision.

Objective—To determine the mode of inheritance for cerebellar abiotrophy (CA), a neurologic disease in Arabians. Animals—804 Arabians, including 29 horses (15 males and 14 females) with CA. Procedures—Most horses (n = 755) belonged to 1 of 4 paternal families. Among the 29 CA-affected horses, all had clinical signs consistent with the disease; the disease was confirmed histologically following euthanasia in 8 horses. From the pedigree information, inbreeding coefficients were calculated for 16 affected horses and compared with coefficients for a subgroup of 16 unaffected horses. Complex segregation analysis was used to determine the effect of a putative Mendelian locus on the development of the disease and the probable mode of inheritance of CA. Results—The mean inbreeding coefficient was 0.0871 for CA-affected and unaffected horses, suggesting that all of the Arabians were inbred to the same degree and that affected horses were not more inbred than were unaffected horses. Results of the complex segregation analysis were consistent with a single Mendelian autosomal recessive mode of inheritance. Conclusions and Clinical Relevance—Knowledge of the mode of inheritance of CA should help breeders to make informed decisions regarding the selection of animals for mating when closely related horses have developed CA or produced CA-affected foals.

Objective-To inoculate white-tailed deer (Odocoileus virginianus) during the sixth or seventh week of gestation with bovine viral diarrhea virus (BVDV) and observe for signs of reproductive tract disease during a 182-day period. Animals-10 pregnant white-tailed deer (8 seronegative and 2 seropositive [control deer] for BVDV). Procedures-Deer were inoculated with 1 of 2 deer-derived BVDV strains (RO3-20663 or RO3-24272). Serum anti-BVDV antibody titers were determined prior to and 21 or 35 days after inoculation. Virus isolation (VI) procedures were performed on tissues from fetuses and does that died and on blood samples collected from live fawns. Ear notch specimens obtained from live fawns were assessed by use of BVDV antigen-capture ELISA (ACE). Results-Both RO3-20663-inoculated seropositive deer gave birth to apparently normal fawns. Among the RO3-24272-inoculated seronegative deer, 1 died, and 1 aborted and 1 resorbed their fetuses; among the RO3-20663-inoculated seronegative deer, 3 died, 1 aborted its fetus, and 1 gave birth to 2 fawns that were likely persistently infected. On the basis of VI and ACE results, those 2 fawns were positive for BVDV; both had no detectable neutralizing anti-BVDV antibodies in serum. Conclusions and Clinical Relevance-Reproductive tract disease that developed in pregnant white-tailed deer following BVDV inoculation was similar to that which develops in BVDV-exposed cattle. Methods developed for BVDV detection in cattle (VI, immunohistochemical evaluations, and ACE) can be applied in assessments of white-tailed deer. Fawns from does that had serum anti-BVDV antibodies prior to inoculation were protected against BVDV infection in utero.