Objective—To assess effects of treatment with phenylbutazone (PBZ) or a combination of PBZ and flunixin meglumine in horses.
Animals—24 adult horses.
Procedure—13 horses received nonsteroidal antiinflammatory drugs (NSAIDs) in a crossover design. Eleven control horses were exposed to similar environmental conditions. Treated horses received PBZ (2.2 mg/kg, PO, q 12 h, for 5 days) and a combination of PBZ and flunixin meglumine (PBZ, 2.2 mg/kg, PO, q 12 h, for 5 days; flunixin meglumine, 1.1 mg/kg, IV, q 12 h, for 5 days). Serum samples were obtained on day 0 (first day of treatment) and day 5, and total protein, albumin, and globulin were measured.
Results—1 horse was euthanatized with severe hypoproteinemia, hypoalbuminemia, and colitis during the combination treatment. Comparisons revealed no significant difference between control horses and horses treated with PBZ alone. There was a significant difference between control and treated horses when administered a combination of PBZ and flunixin meglumine. Correction for horses with values >2 SDs from the mean revealed a significant difference between control horses and horses administered the combination treatment, between control horses and horses administered PBZ alone, and between horses receiving the combination treatment and PBZ alone. Gastroscopy of 4 horses revealed substantial gastric ulcers when receiving the combination NSAID treatment.
Conclusions and Clinical Relevance—Analysis of results of the study indicates the need for caution when administering a combination NSAID treatment to horses because the detrimental effects may outweigh any potential benefits.
Objective—To evaluate 3 refractometers for detection
of failure of passive transfer (FPT) of immunity in calves,
and assess the effect of refractometric test endpoints
on sensitivity, specificity, and proportion of calves classified
correctly with regard to passive transfer status.
Procedure—Blood samples were obtained from calves
that were < 10 days old. Serum IgG concentration was
determined by use of a radial immunodiffusion assay.
Accuracy of 3 refractometers in the prediction of serum
IgG concentration was determined by use of standard
epidemiologic methods and a linear regression model.
Results—At a serum protein concentration test endpoint
of 5.2 g/dL, sensitivity of each refractometer
was 0.89 or 0.93, and specificity ranged from 0.80 to
0.91. For all refractometers, serum protein concentration
test endpoints of 5.0 or 5.2 g/dL resulted in sensitivity
> 0.80, specificity > 0.80, and proportion of
calves classified correctly > 0.85. Serum protein concentrations
equivalent to 1,000 mg of IgG/dL of serum
were 4.9, 4.8, and 5.1 g/dL for the 3 refractometers.
Conclusions and Clinical Relevance—The refractometers,
including a nontemperature-compensating
instrument, performed similarly in detection of FPT.
Serum protein concentration test endpoints of 5.0
and 5.2 g/dL yielded accurate results in the assessment
of adequacy of passive transfer; lower or higher
test endpoints misclassified larger numbers of
calves. (J Am Vet Med Assoc 2002;221:1605–1608)
Objective—To determine the disposition of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and lung tissue homogenate in cattle.
Animals—33 healthy Angus calves approximately 7 to 8 months of age.
Procedures—Calves were randomly assigned to 1 of 11 groups consisting of 3 calves each, which differed with respect to sample collection times. In 10 groups, 1 dose of gamithromycin (6 mg/kg) was administered SC in the neck of each calf (0 hours). The remaining 3 calves were not treated. Gamithromycin concentrations in plasma, PELF, lung tissue homogenate, and BAL cells (matrix) were measured at various points by means of high-performance liquid chromatography with tandem mass spectrometry.
Results—Time to maximum gamithromycin concentration was achieved at 1 hour for plasma, 12 hours for lung tissue, and 24 hours for PELF and BAL cells. Maximum gamithromycin concentration was 27.8 μg/g, 17.8 μg/mL, 4.61 μg/mL, and 0.433 μg/mL in lung tissue, BAL cells, PELF, and plasma, respectively. Terminal half-life was longer in BAL cells (125.0 hours) than in lung tissue (93.0 hours), plasma (62.0 hours), and PELF (50.6 hours). The ratio of matrix to plasma concentrations ranged between 4.7 and 127 for PELF, 16 and 650 for lung tissue, and 3.2 and 2,135 for BAL cells.
Conclusions and Clinical Relevance—Gamithromycin was rapidly absorbed after SC administration. Potentially therapeutic concentrations were achieved in PELF, BAL cells, and lung tissue within 30 minutes after administration and persisted for 7 (PELF) to > 15 (BAL cells and lung tissue) days after administration of a single dose.
Objective—To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally.
Animals—6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2.
Procedures—In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma and urine samples were obtained and analyzed. In a second experiment, 12 horses received IV injections of firocoxib solution once daily for 9 consecutive days, and plasma was obtained and analyzed.
Results—Mean ± SD clearance and steady-state volume of distribution of firocoxib were 40.5 ± 14.7 mL/h/kg and 2.3 ± 0.7 L/kg, respectively. Mean half-life was 44.2 ± 21.6 hours and 36.5 ± 9.5 hours for IV and oral administration, respectively. The urine concentration– time curve decreased in parallel with the plasma concentration-verus-time curve. Renal clearance (0.26 ± 0.09 mL/kg/h) was low, compared with total body clearance, which indicated that the main route of elimination was hepatic clearance.
Conclusions and Clinical Relevance—The pharmacokinetics of firocoxib during prolonged use were determined. Use of plasma or urine to ascertain drug concentrations in horses is scientifically valid because the plasma-to-urine ratio was consistent over time and among horses.
Objective—To determine the relationship between
serum and liver copper concentrations and evaluate
serum copper determination for diagnosis of copper
deficiency in juvenile beef calves.
Animals—105 juvenile beef calves.
Procedure—Copper concentrations were measured
in paired liver and serum samples from 6- to 9-monthold
beef calves. Regression models that predicted
liver copper concentration as a function of serum copper
concentration were developed. Sensitivity and
specificity of serum copper concentration for detection
of low liver copper concentration were determined,
using a range of serum copper concentrations
as test endpoints. Positive and negative predictive values
Results—The association between serum and liver
copper concentrations was significant; however,
regression models accounted for only a small portion
of the variation in liver copper concentrations. For a
serum copper concentration endpoint of 0.45 µg/g,
sensitivity and specificity for detection of low liver
copper concentration were 0.53 and 0.89, respectively.
Positive and negative predictive values of serum
copper concentration for detection of low liver copper
concentration ranged from 0.37 to 0.85 and 0.63 to
Conclusions and Clinical Relevance—Regression
models are inappropriate for predicting copper status
as a function of serum copper concentration. Serum
copper concentration is fairly specific for detection of
low liver copper concentration but only marginally
sensitive when serum copper concentration of 0.45
µg/g is used as a test endpoint. The value of serum
copper concentration as a diagnostic indicator
depends on prevalence of copper deficiency. (J Am
Vet Med Assoc 2001;218:756–760)
Objective—To determine the pharmacokinetic disposition of IV administered caffeine in healthy Lama spp camelids.
Animals—4 adult male alpacas and 4 adult female llamas.
Procedures—Caffeine (3 mg/kg) was administered as an IV bolus. Plasma caffeine concentrations were determined by use of high-performance liquid chromatography in 6 animals and by use of liquid chromatography-mass spectrometry in 2 llamas.
Results—Median elimination half-life was 11 hours (range, 9.3 to 29.8 hours) in alpacas and 16 hours (range, 5.4 to 17 hours) in llamas. The volume of distribution at steady state was 0.60 L/kg (range, 0.45 to 0.93 L/kg) in alpacas and 0.75 L/kg (range, 0.68 to 1.15 L/kg) in llamas. Total plasma clearance was 44 mL/h/kg (range, 24 to 56 mL/h/kg) in alpacas and 42 mL/h/kg (range, 30 to 109 mL/h/kg) in llamas.
Conclusions and Clinical Relevance—High-performance liquid chromatography and liquid chromatography-mass spectrometry were suitable methods for determination of plasma caffeine concentrations in alpacas and llamas. Plasma caffeine concentration-time curves were best described by a 2-compartment model. Elimination half-lives, plasma clearance, volume of distribution at steady state, and mean residence time were not significantly different between alpacas and llamas. Intravenous administration of caffeine at a dose of 3 mg/kg did not induce clinical signs of excitement.