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Abstract

OBJECTIVE

To identify an oral dose of grapiprant for red-tailed hawks (RTHAs; Buteo jamaicensis) that would achieve a plasma concentration > 164 ng/mL, which is considered therapeutic for dogs with osteoarthritis.

ANIMALS

6 healthy adult RTHAs.

PROCEDURES

A preliminary study, in which grapiprant (4 mg/kg [n = 2], 11 mg/kg [2], or 45 mg/kg [2]) was delivered into the crop of RTHAs from which food had been withheld for 24 hours, was performed to obtained pharmacokinetic data for use with modeling software to simulate results for grapiprant doses of 20, 25, 30, 35, and 40 mg/kg. Simulation results directed our selection of the grapiprant dose administered to the RTHAs in a single-dose study. Plasma grapiprant concentration, body weight, and gastrointestinal signs of RTHAs were monitored.

RESULTS

On the basis of results from the preliminary study and simulations, a grapiprant dose of 30 mg/kg was used in the single-dose study. The geometric mean maximum observed plasma concentration of grapiprant was 3,184 ng/mL, time to maximum plasma grapiprant concentration was 2.0 hours, and the harmonic mean terminal half-life was 17.1 hours. No substantial adverse effects were observed.

CONCLUSIONS AND CLINICAL RELEVANCE

Although the single dose of grapiprant (30 mg/kg) delivered into the crop achieved plasma concentrations > 164 ng/mL in the RTHAs, it was unknown whether this concentration would be therapeutic for birds. Further research that incorporates multidose assessments, safety monitoring, and pharmacodynamic data collection is warranted on the use of grapiprant in RTHAs from which food was withheld versus not withheld.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine the pharmacokinetics and sedative effects of 2 doses of a concentrated buprenorphine formulation after SC administration to red-tailed hawks (Buteo jamaicensis).

ANIMALS 6 adult red-tailed hawks.

PROCEDURES Concentrated buprenorphine (0.3 mg/kg, SC) was administered to all birds. Blood samples were collected at 10 time points over 24 hours after drug administration to determine plasma buprenorphine concentrations. After a 4-week washout period, the same birds received the same formulation at a higher dose (1.8 mg/kg, SC), and blood samples were collected at 13 time points over 96 hours. Hawks were monitored for adverse effects and assigned agitation-sedation scores at each sample collection time. Plasma buprenorphine concentrations were quantified by liquid chromatography–tandem mass spectrometry.

RESULTS Mean time to maximum plasma buprenorphine concentration was 7.2 minutes and 26.1 minutes after administration of the 0.3-mg/kg and 1.8-mg/kg doses, respectively. Plasma buprenorphine concentrations were > 1 ng/mL for mean durations of 24 and 48 hours after low- and high-dose administration, respectively. Mean elimination half-life was 6.23 hours for the low dose and 7.84 hours for the high dose. Mean agitation-sedation scores were higher (indicating some degree of sedation) than the baseline values for 24 hours at both doses. No clinically important adverse effects were observed.

CONCLUSIONS AND CLINICAL RELEVANCE Concentrated buprenorphine was rapidly absorbed, and plasma drug concentrations considered to have analgesic effects in other raptor species were maintained for extended periods. Most birds had mild to moderate sedation. Additional studies are needed to evaluate the pharmacodynamics of these doses of concentrated buprenorphine in red-tailed hawks.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the pharmacokinetic parameters of hydromorphone hydrochloride and its metabolite, hydromorphone-3-glucuronide (H3G), after a single IV and IM dose in great horned owls (Bubo virginianus).

ANIMALS

6 healthy adult great horned owls (3 females and 3 males).

PROCEDURES

A single dose of hydromorphone (0.6 mg/kg) was administered once IM (pectoral muscles) and IV (left jugular) with a 6-week washout period between experiments. Blood samples were collected at 5 minutes and 0.5, 1.5, 2, 3, 6, 9, and 12 hours after drug administration. Plasma hydromorphone and H3G concentrations were determined with liquid chromatography–tandem mass spectrometry, and a noncompartmental analysis was used for the determination of pharmacokinetic parameters.

RESULTS

Hydromorphone had a high bioavailability of 170.8 ± 37.6% and rapid elimination after IM administration and rapid plasma clearance and a large volume of distribution after IV administration. Mean Cmax was 225.46 ± 0.2 ng/mL at 13 minutes after IM injection. Mean volume of distribution and plasma drug clearance was 4.29 ± 0.5 L/kg and 62.11 ± 14.6 mL/min/kg, respectively, after IV administration. Mean t1/2 was 1.62 ± 0.36 and 1.35 ± 0.59 hours after IM and IV administration, respectively. The metabolite H3G was readily measured shortly after administration by both routes.

CLINICAL RELEVANCE

A single dose of 0.6 mg/kg was well tolerated in all birds. Hydromorphone rapidly attained plasma concentrations following IM administration and had high bioavailability and short t1/2. This study is the first to document the presence of the metabolite H3G in avian species, which suggests similar hydromorphone metabolism as in mammals.

Open access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effects of dorsal versus lateral recumbency on the cardiopulmonary system during isoflurane anesthesia in red-tailed hawks (Buteo jamaicensis).

Animals—6 adult 1.1- to 1.6-kg red-tailed hawks.

Procedures—A randomized, crossover study was used to evaluate changes in respiratory rate, tidal volume, minute ventilation, heart rate, mean arterial and indirect blood pressures, and end-tidal Pco2 measured every 5 minutes plus Paco2 and Pao2 and arterial pH measured every 15 minutes throughout a 75-minute study period.

Results—Respiratory rate was higher, tidal volume lower, and minute ventilation not different in lateral versus dorsal recumbency. Position did not affect heart rate, mean arterial blood pressure, or indirect blood pressure, although heart rate decreased during the anesthetic period. Birds hypoventilated in both positions and Paco2 differed with time and position × time interaction. The Petco2 position × time interaction was significant and Petco2 was a mean of 7 Torr higher than Paco2. The Paco2 in dorsal recumbency was a mean of 32 Torr higher than in lateral recumbency. Birds in both positions developed respiratory acidosis.

Conclusions and Clinical Relevance—Differences in tidal volume with similar minute ventilation suggested red-tailed hawks in dorsal recumbency might have lower dead space ventilation. Despite similar minute ventilation in both positions, birds in dorsal recumbency hypoventilated more yet maintained higher Pao2, suggesting parabronchial ventilatory or pulmonary blood flow distribution changes with position. The results refute the hypothesis that dorsal recumbency compromises ventilation and O2 transport more than lateral recumbency in red-tailed hawks.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effects of 4.7-mg deslorelin acetate implants on egg production and plasma concentrations of 17β-estradiol and androstenedione in Japanese quail (Coturnix coturnix japonica) over 180 days and assess safety of the implants in quail via gross and histologic examination.

Animals—20 female Japanese quail.

Procedures—Following a 7-day period of consistent egg laying, quail were anesthetized and received a 4.7-mg deslorelin implant (treatment group; n = 10) or identical placebo implant (control group; 10) SC between the scapulae. Egg production was monitored daily. Plasma concentrations of 17β-estradiol and androstenedione were measured on days 0 (immediately prior to implant injection), 14, 29, 62, 90, 120, 150, and 180 via radioimmunoassay. Birds were weighed periodically and euthanized at day 180 for complete necropsy.

Results—Egg production was significantly decreased in the treatment group, compared with the control group, from 2 to 12 weeks after implant injection. Egg production ceased in 6 of 10 quail in the treatment group (mean duration of cessation, 70 days). Plasma androstenedione and 17β-estradiol concentrations were significantly lower on day 29 in the treatment group than in the control group. Plama androstenedione and 17β-estradiol concentrations were significantly lower on day 29 in the treatment group then in the control group.

Conclusions and Clinical Relevance—4.7-mg deslorelin acetate implants reversibly decreased egg laying for approximately 70 days in most of the Japanese quail evaluated. Further studies evaluating implants containing different concentrations of the drug are needed in quail and other avian species.

Full access
in American Journal of Veterinary Research

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.

Full access
in American Journal of Veterinary Research

Abstract

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 owls.

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)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of body position on lung and air-sac volumes in anesthetized and spontaneously breathing red-tailed hawks (Buteo jamaicensis).

Animals—6 adult red-tailed hawks (sex unknown).

Procedures—A crossover study design was used for quantitative estimation of lung and air-sac volumes in anesthetized hawks in 3 body positions: dorsal, right lateral, and sternal recumbency. Lung volume, lung density, and air-sac volume were calculated from helical computed tomographic (CT) images by use of software designed for volumetric analysis of CT data. Effects of body position were compared by use of repeated-measures ANOVA and a paired Student t test.

Results—Results for all pairs of body positions were significantly different from each other. Mean ± SD lung density was lowest when hawks were in sternal recumbency (–677 ± 28 CT units), followed by right lateral (–647 ± 23 CT units) and dorsal (–630 ± 19 CT units) recumbency. Mean lung volume was largest in sternal recumbency (28.6 ± 1.5 mL), followed by right lateral (27.6 ± 1.7 mL) and dorsal (27.0 ± 1.5 mL) recumbency. Mean partial air-sac volume was largest in sternal recumbency (27.0 ± 19.3 mL), followed by right lateral (21.9 ± 16.1 mL) and dorsal (19.3 ± 16.9 mL) recumbency.

Conclusions and Clinical Relevance—In anesthetized red-tailed hawks, positioning in sternal recumbency resulted in the greatest lung and air-sac volumes and lowest lung density, compared with positioning in right lateral and dorsal recumbency. Additional studies are necessary to determine the physiologic effects of body position on the avian respiratory system.

Full access
in American Journal of Veterinary Research

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.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To test the hypothesis that differences in anesthetic uptake and elimination in iguanas would counter the pharmacokinetic effects of blood:gas solubility and thus serve to minimize kinetic differences among inhaled agents.

Animals—6 green iguanas (Iguana iguana).

Procedures—Iguanas were anesthetized with isoflurane, sevoflurane, or desflurane in a Latin-square design. Intervals from initial administration of an anesthetic agent to specific induction events and from cessation of administration of an anesthetic agent to specific recovery events were recorded. End-expired gas concentrations were measured during anesthetic washout.

Results—Significant differences were not detected for any induction or recovery events for any inhalation agent in iguanas. Washout curves best fit a 2-compartment model, but slopes for both compartments did not differ significantly among the 3 anesthetics.

Conclusions and Clinical Relevance—Differences in blood:gas solubility for isoflurane, sevoflurane, and desflurane did not significantly influence differences in pharmacokinetics for the inhalation agents in iguanas.

Full access
in American Journal of Veterinary Research