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- Author or Editor: Joanne R. Paul-Murphy x
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Abstract
OBJECTIVE
To evaluate the pharmacokinetics of hydromorphone hydrochloride after IM and IV administration to orange-winged Amazon parrots (Amazona amazonica).
ANIMALS
8 orange-winged Amazon parrots (4 males and 4 females).
PROCEDURES
Hydromorphone (1 mg/kg) was administered once IM. Blood samples were collected 5 minutes and 0.5, 1.5, 2, 3, 6, and 9 hours after drug administration. Plasma hydromorphone concentrations were determined with liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated with a compartmental model. The experiment was repeated 1 month later with the same dose of hydromorphone administered IV.
RESULTS
Plasma hydromorphone concentrations were > 1 ng/mL for 6 hours in 8 of 8 and 6 of 7 parrots after IM and IV injection, respectively. After IM administration, mean bioavailability was 97.6%, and mean maximum plasma concentration was 179.1 ng/mL 17 minutes after injection. Mean volume of distribution and plasma drug clearance were 4.24 L/kg and 64.2 mL/min/kg, respectively, after IV administration. Mean elimination half-lives were 1.74 and 1.45 hours after IM and IV administration, respectively.
CONCLUSIONS AND CLINICAL RELEVANCE
Hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with rapid plasma clearance and a large volume of distribution after IV administration in orange-winged Amazon parrots. Drug elimination half-lives were short. Further pharmacokinetic studies of hydromorphone and its metabolites, including investigation of multiple doses, different routes of administration, and sustained-release formulations, are recommended.
Abstract
OBJECTIVE To determine pharmacokinetics and sedative effects of buprenorphine after IV and oral transmucosal (OTM) administration in guinea pigs.
ANIMALS 14 male guinea pigs (6 adults for preliminary experiment; eight 8 to 11-week-old animals for primary study).
PROCEDURES A preliminary experiment was conducted to determine an appropriate buprenorphine dose. In the primary study, buprenorphine (0.2 mg/kg) was administered IV or OTM, and blood samples were obtained. The pH of the oral cavity was measured before OTM administration. Sedation was scored for 6 hours on a scale of 0 to 3 (0 = no sedation and 3 = heavy sedation). After a 7-day washout period, procedures were repeated in a crossover manner. Plasma buprenorphine concentration was quantified, and data were analyzed with a noncompartmental pharmacokinetic approach.
RESULTS Mean peak plasma buprenorphine concentrations were 46.7 and 2.4 ng/mL after IV and OTM administration, respectively. Mean time to maximum plasma buprenorphine concentration was 1.5 and 71.2 minutes, and mean terminal half-life was 184.9 and 173.0 minutes for IV and OTM administration, respectively. There was a range of sedation effects (0 to 2) for both routes of administration, which resolved within the 6-hour time frame.
CONCLUSIONS AND CLINICAL RELEVANCE On the basis of pharmacokinetic parameters for this study, buprenorphine at 0.2 mg/kg may be administered IV every 7 hours or OTM every 4 hours to maintain a target plasma concentration of 1 ng/mL. Further studies are needed to evaluate administration of multiple doses and sedative effects in guinea pigs with signs of pain.
Abstract
Objective—To establish an objective method of determining proventricular diameter in psittacine birds by assessment of lateral whole-body radiographic views.
Design—Retrospective case-control study.
Animals—100 parrots with no signs of gastric disease and 19 parrots with signs of gastric disease.
Procedures—Measurements were obtained for the following variables: proventricular diameter at the level of the junction between the last thoracic vertebra and synsacrum, maximum distance between the dorsal serosa of the proximal aspect of the proventriculus and dorsal border of the sternum, maximum coelomic cavity height at the level of the proximal aspect of the proventriculus, and maximum dorsoventral height of the keel of the sternum. The ratio of proventricular diameter to each of those measurements was calculated and compared among species within the group without signs of gastric disease and between the gastric and nongastric disease groups.
Results—No significant differences were seen among species of parrots without signs of gastric disease for any ratio, but there were significant differences between parrots with gastric signs and those without gastric signs for all ratios. Only the proventricular diameterto-maximum dorsoventral height of the keel of the sternum ratio had no numeric overlap between groups. Sensitivity and specificity of the ratio for detection of proventricular enlargement were both 100%. Six causes associated with proventricular enlargement were identified.
Conclusions and Clinical Relevance—Evaluation of the proventricular diameter-to-keel height ratio is a new method for evaluating proventricular size in psittacines. Ratio values < 0.48 indicate normal proventricular diameter and the absence of proventricular disease.
Abstract
OBJECTIVE
To characterize clinical and pathological findings of rabbits evaluated at a veterinary teaching hospital because of dystocia.
DESIGN
Retrospective case series.
ANIMALS
9 client-owned rabbits and 1 wild rabbit with signs of dystocia evaluated at a veterinary teaching hospital from 1996 through 2016.
PROCEDURES
Medical records of rabbits were reviewed to collect data on signalment; medical history; physical examination, laboratory, diagnostic imaging, and procedural findings; treatment; final diagnosis; and outcome. Data were summarized.
RESULTS
Dystocia in 7 rabbits was successfully managed through medical treatment, assisted vaginal delivery, or both (n = 6) or surgery alone (1); 3 rabbits were euthanized. Primiparous does, does ≤ 4 years old, and does of small breeds (< 2 kg [4.4 lb]) were most common. All client-owned rabbits had clinical signs of abnormal second-stage parturition, whereas the wild rabbit had only hemorrhagic vulvar discharge. Imaging was used to identify the number, size, and state of fetuses in most rabbits. Overall, 35 fetuses were accounted for, 25 of which were dead or later died. The cause of dystocia was determined for 8 rabbits and included fetal-maternal mismatch (n = 4), uterine inertia (2), fetal death or mummification (1), and stress-induced abortion (1).
CONCLUSIONS AND CLINICAL RELEVANCE
Obstructive dystocia from fetal macrosomia with or without secondary uterine inertia was the most common cause of dystocia in the evaluated rabbits. Although medical management was successful for many rabbits with dystocia in this study, surgery could still be required in other affected rabbits, particularly when fetal-maternal mismatch is involved.
Abstract
OBJECTIVE
To determine the pharmacokinetics of amantadine after oral administration of single and multiple doses to orange-winged Amazon parrots (Amazona amazonica).
ANIMALS
12 adult orange-winged Amazon parrots (6 males and 6 females).
PROCEDURES
A single dose of amantadine was orally administered to 6 birds at 5 mg/kg (n = 2), 10 mg/kg (2), and 20 mg/kg (2) in a preliminary trial. On the basis of the results, a single dose of amantadine (10 mg/kg, PO) was administered to 6 other birds. Two months later, multiple doses of amantadine (5 mg/kg, PO, q 24 h for 7 days) were administered to 8 birds. Heart rate, respiratory rate, behavior, and urofeces were monitored. Plasma concentrations of amantadine were measured via tandem liquid chromatography–mass spectrometry. Pharmacokinetic parameter estimates were determined via noncompartmental analysis.
RESULTS
Mean ± SD maximum plasma concentration, time to maximum plasma concentration, half-life, and area under the concentration-versus-time curve from the last dose to infinity were 1,174 ± 186 ng/mL, 3.8 ± 1.8 hours, 23.2 ± 2.9 hours, and 38.6 ± 7.4 μg·h/mL, respectively, after a single dose and 1,185 ± 270 ng/mL, 3.0 ± 2.4 hours, 21.5 ± 5.3 hours, and 26.3 ± 5.7 μg·h/mL, respectively, at steady state after multiple doses. No adverse effects were observed.
CONCLUSIONS AND CLINICAL RELEVANCE
Once-daily oral administration of amantadine at 5 mg/kg to orange-winged Amazon parrots maintained plasma concentrations above those considered to be therapeutic in dogs. Further studies evaluating safety and efficacy of amantadine in orange-winged Amazon parrots are warranted.
Abstract
OBJECTIVE To determine pharmacokinetics of butorphanol tartrate incorporated into poloxamer 407 (P407) after SC administration to Hispaniolan Amazon parrots (Amazona ventralis).
ANIMALS 11 adult Hispaniolan Amazon parrots (6 males and 5 females; 11 to 27 years old).
PROCEDURES A sterile formulation of butorphanol in P407 (But-P407) 25% (percentage determined as [weight of P407/weight of diluent] × 100]) was created (8.3 mg/mL). Five preliminary experiments (2 birds/experiment) were performed to determine the ideal dose for this species. The formulation then was administered (12.5 mg/kg, SC) to 8 birds. Blood samples were collected before (time 0) and 0.08, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Some birds were used more than once, with a washout period of ≥ 3 months between subsequent treatments. Butorphanol concentrations were quantitated by use of liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was performed by use of noncompartmental analysis.
RESULTS Maximal plasma butorphanol concentration was reached at 1.31 hours. Plasma concentrations of butorphanol remained > 100 ng/mL for > 3 hours (all birds) or > 4 hours (5/8 birds) but < 8 hours (all birds). Half-life of the terminal slope was 3.41 hours. No adverse effects were detected.
CONCLUSIONS AND CLINICAL RELEVANCE Butorphanol was absorbed well from the But-P407 25% by Hispaniolan Amazon parrots, and absorption followed a pharmacokinetic profile compatible with a sustained-release drug. A dose of 12.5 mg/kg, SC, would theoretically provide analgesia for 4 to 8 hours. No adverse effects were detected. Studies on the pharmacodynamics of this formulation are necessary to confirm the degree and duration of analgesia.
Abstract
OBJECTIVE To evaluate thermal antinociceptive effects and pharmacokinetics of buprenorphine hydrochloride after IM administration to cockatiels (Nymphicus hollandicus).
ANIMALS 16 adult (≥ 2 years old) cockatiels (8 males and 8 females).
PROCEDURES Buprenorphine hydrochloride (0.3 mg/mL) at each of 3 doses (0.6, 1.2, and 1.8 mg/kg) and saline (0.9% NaCl) solution (control treatment) were administered IM to birds in a randomized within-subject complete crossover study. Foot withdrawal response to a thermal stimulus was determined before (baseline) and 0.5, 1.5, 3, and 6 hours after treatment administration. Agitation-sedation scores were also determined. For the pharmacokinetic analysis, buprenorphine (0.6 mg/kg) was administered IM to 12 of the birds, and blood samples were collected at 9 time points ranging from 5 minutes to 9 hours after drug administration. Samples were analyzed with liquid chromatography–mass spectrometry. Pharmacokinetic parameters were calculated with commercial software.
RESULTS Buprenorphine at 0.6, 1.2, and 1.8 mg/kg did not significantly change the thermal foot withdrawal response, compared with the response for the control treatment. No significant change in agitation-sedation scores was detected between all doses of buprenorphine and the control treatment. Plasma buprenorphine concentrations were > 1 ng/mL in all 4 birds evaluated at 9 hours.
CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine at the doses evaluated did not significantly change the thermal nociceptive threshold for cockatiels or cause sedative or agitative effects. Additional studies with other pain assessments and drug doses are needed to evaluate the analgesic and adverse effects of buprenorphine in cockatiels and other avian species.
Abstract
OBJECTIVES
To determine the pharmacokinetics of butorphanol tartrate incorporated into poloxamer 407 (P407) after subcutaneous administration to orange-winged Amazon parrots (Amazona amazonica).
ANIMALS
Six orange-winged Amazon parrots, ages 28 to 45 years.
PROCEDURES
A sterile formulation of butorphanol in P407 (But-P407) as a 25% gel was created to produce a concentration of 8.3 mg/mL. The formulation was administered SC at a dose of 12.5 mg/kg to all birds. Blood samples were collected at baseline prior to injection (time 0) and then at 0.08, 0.5, 1, 1.5, 4, 8, and 12 hours after drug administration. Butorphanol concentrations were quantitated via liquid chromatography–tandem mass spectrometry. Pharmacokinetic analysis was performed using noncompartmental analysis and a commercially available software program.
RESULTS
Plasma concentrations of butorphanol remained > 100 ng/mL for > 4 hours for some birds (3/5) but were < 100 ng/mL for all birds by the 8-hour mark. Cmax and tmax were 346.9 ± 233.7 ng/mL and 1.3 ± 0.274 hours, respectively. Half-life was 1.56 ± 0.445 hours. No adverse effects were detected.
CLINICAL RELEVANCE
Butorphanol was absorbed from the But-P407 25% by the majority of the orange-winged Amazon parrots in this study (3/5), although to a lesser extent compared to Hispaniolan Amazon parrots. Absorption followed a pharmacokinetic profile compatible with a sustained-release drug. A dose of 12.5 mg/kg, SC, would be expected to provide antinociception for 4 to 8 hours, although pharmacodynamic studies in this species using this formulation have not demonstrated this.
Abstract
OBJECTIVE
Describe the pharmacokinetics of grapiprant administered orally with food to red-tailed hawks (RTHAs; Buteo jamaicensis) and compare the results with previously described grapiprant pharmacokinetics administered without food in this species.
ANIMALS
6 healthy adult RTHA (3 males, 3 females) under human care.
PROCEDURES
A single dose of grapiprant (30 mg/kg) was given orally to RTHAs, followed by force-feeding. Blood samples were obtained at 14 time points for 120 hours postgrapiprant administration. Plasma concentrations of grapiprant were measured via tandem liquid chromatography-mass spectrometry. Nonparametric superimposition using pharmacokinetic modeling software used plasma concentrations to calculate simulations of grapiprant plasma concentrations for 30 mg/kg administered orally with food every 12 hours.
RESULTS
The arithmetic mean maximum plasma concentration was 405.8 ng/mL, time to maximum plasma concentration was 16 hours, and harmonic mean terminal half-life was 15.6 hours. Simulations determined 30 mg/kg every 12 hours could attain minimum effective concentrations (> 164 ng/mL) reported in dogs for a sustained period of approximately 20 hours.
CLINICAL RELEVANCE
Grapiprant plasma concentrations were achieved above the canine therapeutic concentrations within 16 hours postmedication. Mean concentrations were maintained for approximately 20 hours. Simulations support a dosing frequency of 12-hour intervals with food reaching minimum effective concentrations established for canines, although it is unknown whether these plasma concentrations are therapeutic for birds. Bioaccumulation was not noted on simulations secondary to increased grapiprant administration. Further research including multidose assessments at this current dose with food, in vitro pharmacological characterization, and pharmacodynamic studies in this species are warranted.
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.
