OBJECTIVE To determine the pharmacokinetics of voriconazole administered PO with or without food to red-tailed hawks (Buteo jamaicensus) and whether any observed variability could be explained by measured covariates to inform dose adjustments.
ANIMALS 7 adult red-tailed hawks.
PROCEDURES In a crossover study design, hawks were randomly assigned to first receive voriconazole (15 mg/kg, PO) injected into a dead mouse (n = 3; fed birds) or without food (4; unfed birds). Sixteen days later, treatments were reversed. Blood samples were collected at various points to measure plasma voriconazole concentrations by ultraperformance liquid chromatography. Pharmacokinetic data were analyzed by noncompartmental methods and fit to a compartmental model through nonlinear mixed-effects regression, with feeding status and body weight investigated as covariates.
RESULTS Voriconazole was well absorbed, with quantifiable plasma concentrations up to 24 hours after administration. Mean plasma half-life was approximately 2 hours in fed and unfed birds. Administration of the voriconazole in food delayed absorption, resulting in a significant delay in time to maximum plasma concentration. The final compartmental model included a categorical covariate to account for this lag in absorption as well as body weight as a covariate of total body clearance (relative to unknown bioavailability).
CONCLUSIONS AND CLINICAL RELEVANCE A single dose of voriconazole (15 mg/kg) administered PO to red-tailed hawks resulted in mean plasma voriconazole concentrations greater than the targeted value (1 μg/mL). Additional studies with larger sample sizes and multidose regimens are required before the model developed here can be applied in clinical settings.
Objective—To evaluate flow cytometric analysis for
sex identification in 3 psittacine species, establish reference
values for blood cell DNA content for each
species, and determine effects of sample storage on
Animals—36 orange-winged Amazon parrots, 41
budgerigars, and 39 cockatiels.
Procedure—Blood samples were stained and analyzed
by use of flow cytometry to measure cellular
DNA content. Samples were analyzed immediately
after collection and after being stored at 4 C for 48
and 72 hours.
Results—Mean DNA content (picograms per cell)
was 3.248 for Amazon parrots, 2.702 for budgerigars,
and 2.946 for cockatiels; DNA concentrations in samples
analyzed immediately overlapped in a male and a
female Amazon parrot and among 19 cockatiels. For
budgerigars, DNA overlap between sexes was not
detected in samples analyzed immediately or after
storage for 72 hours. Sex was identified correctly in
94.4% of Amazon parrots, 100% of budgerigars, and
51.3% of cockatiels. For both sexes, DNA content in
samples analyzed immediately was significantly different
from that of stored samples.
Conclusions and Clinical Relevance—Flow cytometric
analysis was accurate for sex identification of
Amazon parrots and budgerigars. Sample storage at 4
C for 48 or 72 hours caused variability in DNA content.
(Am J Vet Res 2000;61:847–850)
Objective—To compare sensitivity and specificity of cytologic examination and 3 chromogen tests for detection of occult blood in cockatiel (Nymphicus hollandicus) excrement.
Animals—20 adult cockatiels.
Procedures—Pooled blood from birds was divided into whole blood and lysate aliquots. Excrement was mixed with each aliquot in vitro to yield 6 hemoglobin (Hb) concentrations (range, 0.375 to 12.0 mg of Hb/g of excrement). For the in vivo portion of the study, birds were serially gavaged with each aliquot separately at 5 doses of Hb (range, 2.5 to 40 mg/kg). Three chromogen tests and cytologic examination were used to test excrement samples for occult blood. Sensitivity, specificity, and observer agreement were calculated.
Results—In vitro specificity ranged from 85%to 100% for the 3 chromogen tests and was 100% for cytologic examination. Sensitivity was 0% to 35% for cytologic examination and 100% for the 3 chromogen tests on samples containing ≥ 1.5 mg of Hb/g of excrement. In vivo specificity was 100%, 90%, 65%, and 45% for cytologic examination and the 3 chromogen tests, respectively. Sensitivity was 0% to 5% for cytologic examination and ≥ 75% for all 3 chromogen tests after birds received doses of Hb ≥ 20 mg/kg. Observer agreement was lowest for cytologic examination.
Conclusions and Clinical Relevance—Chromogen tests were more useful than cytologic examination for detection of occult blood in cockatiel excrement. The best combination of sensitivity, specificity, and observer agreement was obtained by use of a chromogen test.
Objective—To determine the pharmacokinetics of
ceftiofur sodium after IM and SC administration in
Animals—6 male and 4 female adult green iguanas.
Procedure—In a crossover design, 5 iguanas
received a single dose of ceftiofur sodium (5 mg/kg)
IM, and 5 iguanas received the same dose SC. Blood
samples were taken at 0, 20, and 40 minutes and 1,
2, 4, 8, 24, 48, and 72 hours after administration. After
a 10-week washout period, each iguana was given the
same dose via the reciprocal administration route,
and blood was collected in the same fashion.
Ceftiofur free-acid equivalents were measured via
high-performance liquid chromatography.
Results—The first phase intercepts were significantly
different between the 2 administration routes.
Mean maximum plasma concentration was significantly
higher with the IM (28.6 ± 8.0 µg/mL) than the
SC (18.6 ± 8.3 µg/mL) administration route. There
were no significant differences between terminal halflives
(harmonic mean via IM route, 15.7 ± 4.7 hours;
harmonic mean via SC route, 19.7 ± 6.7 hours) and
mean areas under the curve measured to the last
time point (IM route, 11,722 ± 7,907 µg·h/mL; SC
route, 12,143 ± 9,633 µg·h/mL). Ceftiofur free-acid
equivalent concentrations were maintained ≥ 2 µg/mL
for > 24 hours via both routes.
Conclusions and Clinical Relevance—A suggested
dosing schedule for ceftiofur sodium in green iguanas
for microbes susceptible at > 2 µg/mL would be 5
mg/kg, IM or SC, every 24 hours. (Am J Vet Res 2003;64:1278–1282)
OBJECTIVE To determine the pharmacokinetics and adverse effects at the injection site of ceftiofur crystalline-free acid (CCFA) following IM administration of 1 dose to red-tailed hawks (Buteo jamaicensis).
PROCEDURES In a randomized crossover study, CCFA (10 or 20 mg/kg) was administered IM to each hawk and blood samples were obtained. After a 2-month washout period, administration was repeated with the opposite dose. Muscle biopsy specimens were collected from the injection site 10 days after each sample collection period. Pharmacokinetic data were calculated. Minimum inhibitory concentrations of ceftiofur for various bacterial isolates were assessed.
RESULTS Mean peak plasma concentrations of ceftiofur-free acid equivalent were 6.8 and 15.1 μg/mL for the 10 and 20 mg/kg doses, respectively. Mean times to maximum plasma concentration were 6.4 and 6.7 hours, and mean terminal half-lives were 29 and 50 hours, respectively. Little to no muscle inflammation was identified. On the basis of a target MIC of 1 μg/mL and target plasma ceftiofur concentration of 4 μg/mL, dose administration frequencies for infections with gram-negative and gram-positive organisms were estimated as every 36 and 45 hours for the 10 mg/kg dose and every 96 and 120 hours for the 20 mg/kg dose, respectively.
CONCLUSIONS AND CLINICAL RELEVANCE Study results suggested that CCFA could be administered IM to red-tailed hawks at 10 or 20 mg/kg to treat infections with ceftiofur-susceptible bacteria. Administration resulted in little to no inflammation at the injection site. Additional studies are needed to evaluate effects of repeated CCFA administration.
Objective—To determine the pharmacokinetic properties of 1 IM injection of ceftiofur crystalline-free acid (CCFA) in American black ducks (Anas rubripes).
Animals—20 adult American black ducks (6 in a preliminary experiment and 14 in a primary experiment).
Procedures—Dose and route of administration of CCFA for the primary experiment were determined in a preliminary experiment. In the primary experiment, CCFA (10 mg/kg, IM) was administered to ducks. Ducks were allocated into 2 groups, and blood samples were obtained 0.25, 0.5, 1, 2, 4, 8, 12, 48, 96, 144, 192, and 240 hours or 0.25, 0.5, 1, 2, 4, 8, 24, 72, 120, 168, and 216 hours after administration of CCFA. Plasma concentrations of ceftiofur free acid equivalents (CFAEs) were determined by use of high-performance liquid chromatography. Data were evaluated by use of a naive pooled-data approach.
Results—The area under the plasma concentration versus time curve from 0 hours to infinity was 783 h•μg/mL, maximum plasma concentration observed was 13.1 μg/mL, time to maximum plasma concentration observed was 24 hours, terminal phase half-life was 32.0 hours, time that concentrations of CFAEs were higher than the minimum inhibitory concentration (1.0 μg/mL) for many pathogens of birds was 123 hours, and time that concentrations of CFAEs were higher than the target plasma concentration (4.0 μg/mL) was 73.3 hours.
Conclusions and Clinical Relevance—On the basis of the time that CFAE concentrations were higher than the target plasma concentration, a dosing interval of 3 days can be recommended for future multidose CCFA studies.
Objective—To compare efficacy and safety of meso-
2,3-dimercaptosuccinic acid (DMSA) and Ca EDTA for
treatment of experimentally induced lead toxicosis in
cockatiels ( Nymphicus hollandicus).
Animals—137 (69 females, 68 males) healthy cockatiels
between 6 months and 8 years old.
Procedure—Lead toxicosis was induced by placing
lead shot in the gastrointestinal tract. Treatment with
Ca EDTA (40 mg/kg of body weight, IM, q 12 h), DMSA
(40 or 80 mg/kg, PO, q 12 h), and sodium sulfate salts
(SSS; 0.5 mg/kg, PO, q 48 h) was initiated 4 days after
induction of lead toxicosis. Blood lead concentrations
were determined, using atomic absorption spectrophotometry.
Number of birds surviving and blood
lead concentrations were compared among groups.
Results—In Phase II of the study, administration of
DMSA and Ca EDTA significantly decreased blood
lead concentrations when used alone or in combination
in birds with lead toxicosis. Addition of SSS did
not result in further decreases in lead concentrations.
Eight of 12 (66.7%) birds without lead toxicosis given
80 mg of DMSA/kg did not survive to the end of the
study . Lesions related to treatment with chelating
agents were not detected during necropsy.
Conclusions and Clinical Relevance—DMSA and
Ca EDTA are effective chelating agents in cockatiels.
Because DMSA is administered orally, it may be easier
than other chelating agents for bird owners to
administer at home. However, the narrow margin of
safety of DMSA indicates that this agent should be
used with caution. (Am J Vet Res 2000;61:935–940)
Objective—To assess the use of a caudal external
thoracic artery axial pattern flap to treat sternal cutaneous
wounds in birds.
Animals—16 adult Japanese quail.
Procedure—A cutaneous defect in the region of the
mid-sternum was surgically created in all quail. In 6
quail (group I), an axial pattern flap was created from
the skin of the lateral aspect of the thorax and
advanced over the sternal defect. In 8 quail (group II),
a flap was similarly created and advanced but the flap
vasculature was ligated. All quail were euthanatized at
14 days after surgery and had necropsies performed.
Sections of the flap and the surrounding tissue were
examined histologically to assess flap viability.
Results—All axial pattern flaps in group-I quail had
100% survival. In group II, mean percentage area of
flap survival was 62.5%; mean area of necrosis and
dermal fibrosis of flaps were significantly greater than
that detected in group I. In flaps of group-II quail, neovascularization
in the deep dermis and profound
necrosis of the vascular plexus in the superficial dermis
Conclusions and Clinical Relevance—Results indicated
that the caudal external thoracic artery axial pattern
flap could be used successfully in the treatment
of surgically created sternal cutaneous defects in
quail with no signs of tissue necrosis or adverse
effects overall. Use of this technique to treat selfmutilation
syndromes or application after surgical
debulking of tumors or other masses might be beneficial
in many avian species. (Am J Vet Res
Objective—To determine induction doses, anesthetic
constant rate infusions (CRI), and cardiopulmonary
effects of propofol in red-tailed hawks and great
horned owls and propofol pharmacokinetics in the
owls during CRI.
Animals—6 red-tailed hawks and 6 great horned
Procedure—The CRI dose necessary for a loss of
withdrawal reflex was determined via specific stimuli.
Anesthesia was induced by IV administration of
propofol (1 mg/kg/min) and maintained by CRI at the
predetermined dose for 30 minutes. Heart and respiratory
rates, arterial blood pressures, and blood gas
tensions were obtained in awake birds and at various
times after induction. End-tidal CO2 (ETCO2) concentration
and esophageal temperature were obtained
after induction. Propofol plasma concentrations were
obtained after induction and after completion of the
CRI in the owls. Recovery times were recorded.
Results—Mean ± SD doses for induction and CRI
were 4.48 ± 1.09 mg/kg and 0.48 ± 0.06 mg/kg/min,
respectively, for hawks and 3.36 ± 0.71 mg/kg and
0.56 ± 0.15 mg/kg/min, respectively, for owls.
Significant increases in PaCO2, HCO3, and ETCO2 in
hawks and owls and significant decreases in arterial
pH in hawks were detected. A 2-compartment model
best described the owl pharmacodynamic data.
Recovery times after infusion were prolonged and
varied widely. Central nervous system excitatory
signs were observed during recovery.
Conclusions and Clinical Relevance—Effects on
blood pressure were minimal, but effective ventilation
was reduced, suggesting the need for careful monitoring
during anesthesia. Prolonged recovery periods
with moderate-to-severe excitatory CNS signs may
occur in these species at these doses. (Am J Vet Res 2003;64:677–683)