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- Author or Editor: Lisa A. Tell x
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Abstract
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.
Abstract
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 DNA content.
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)
Abstract
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.
Abstract
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).
ANIMALS 7 adult nonreleasable healthy red-tailed hawks.
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.
Abstract
Objective—To determine the pharmacokinetics of ceftiofur sodium after IM and SC administration in green iguanas.
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)
Abstract
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.
Abstract
Objective—To determine the stability and distribution of voriconazole in 2 extemporaneously prepared (compounded) suspensions stored for 30 days at 2 temperatures.
Sample Population—Voriconazole suspensions (40 mg/mL) compounded from commercially available 200-mg tablets suspended in 1 of 2 vehicles. One vehicle contained a commercially available suspending agent and a sweetening syrup in a 1:1 mixture (SASS). The other vehicle contained the suspending agent with deionized water in a 3:1 mixture (SADI).
Procedures—Voriconazole suspensions (40 mg/mL in 40-mL volumes) were compounded on day 0 and stored at room temperature (approx 21°C) or refrigerated (approx 5°C). To evaluate distribution, room-temperature aliquots of voriconazole were measured immediately after preparation. Refrigerated aliquots were measured after 3 hours of refrigeration. To evaluate stability, aliquots from each suspension were measured at approximately 7-day intervals for up to 30 days. Voriconazole concentration, color, odor, opacity, and pH were measured, and aerobic and anaerobic bacterial cultures were performed at various points.
Results—Drug distribution was uniform (coefficient of variation, < 5%) in both suspensions. On day 0, 87.8% to 93.0% of voriconazole was recovered; percentage recovery increased to between 95.1% and 100.8% by day 7. On subsequent days, up to day 30, percentage recovery was stable (> 90%) for all suspensions. The pH of each suspension did not differ significantly throughout the 30-day period. Storage temperature did not affect drug concentrations at any time, nor was bacterial growth obtained.
Conclusions and Clinical Relevance—Extemporaneously prepared voriconazole in SASS and SADI resulted in suspensions that remained stable for at least 30 days. Refrigerated versus room-temperature storage of the suspensions had no effect on drug stability.
Abstract
Objective—To determine the tissue depletion profile of tulathromycin and determine an appropriate slaughter withdrawal interval in meat goats after multiple SC injections of the drug.
Animals—16 healthy Boer goats.
Procedures—All goats were administered tulathromycin (2.5 mg/kg, SC) twice, with a 7-day interval between doses. Blood samples were collected throughout the study, and goats were euthanized at 2, 5, 10, and 20 days after the second tulathromycin dose. Lung, liver, kidney, fat, and muscle tissues were collected. Concentrations of tulathromycin in plasma and the hydrolytic tulathromycin fragment CP-60,300 in tissue samples were determined with ultrahigh-pressure liquid chromatography–tandem mass spectrometry.
Results—The plasma profile of tulathromycin was biphasic. Absorption was very rapid, with maximum drug concentrations (1.00 ± 0.42 μg/mL and 2.09 ± 1.77 μg/mL following the first and second doses, respectively) detected within approximately 1 hour after injection. Plasma terminal elimination half-life of tulathromycin was 61.4 ± 14.1 hours after the second dose. Half-lives in tissue ranged from 2.4 days for muscle to 9.0 days for lung tissue; kidney tissue was used to determine the withdrawal interval for tulathromycin in goats because it is considered an edible tissue.
Conclusions and Clinical Relevance—On the basis of the tissue tolerance limit in cattle of 5 ppm (μg/g), the calculated withdrawal interval for tulathromycin would be 19 days following SC administration in goats. On the basis of the more stringent guidelines recommended by the FDA, the calculated meat withdrawal interval following tulathromycin administration in goats was 34 days.
