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- Author or Editor: Heather K. DiMaio Knych x
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Objective—To characterize pharmacokinetics and pharmacodynamics of detomidine gel administered sublingually in accordance with label instructions to establish appropriate withdrawal guidelines for horses before competition.
Animals—12 adult racehorses.
Procedures—Horses received a single sublingual administration of 0.04 mg of detomidine/kg. Blood samples were collected before and up to 72 hours after drug administration. Urine samples were collected for 5 days after detomidine administration. Plasma and urine samples were analyzed via liquid chromatography–mass spectrometry, and resulting data were analyzed by use of noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, glucose concentration, PCV, and plasma protein concentration were also assessed following detomidine administration.
Results—Mean ± SD terminal elimination half-life of detomidine was 1.5 ± 1 hours. Metabolite concentrations were below the limit of detection (0.02, 0.1, and 0.5 ng/mL for detomidine, carboxydetomidine, and hydroxydetomidine, respectively) in plasma by 24 hours. Concentrations of detomidine and its metabolites were below the limit of detection (0.05 ng/mL for detomidine and 0.10 ng/mL for carboxydetomidine and hydroxydetomidine) in urine by 3 days. All horses had various degrees of sedation after detomidine administration. Time of onset was ≤ 40 minutes, and duration of sedation was approximately 2 hours. Significant decreases, relative to values at time 0, were detected for chin-to-ground distance and heart rate. There was an increased incidence and exacerbation of preexisting atrioventricular blocks after detomidine administration.
Conclusions and Clinical Relevance—A 48-hour and 3-day withdrawal period for detection in plasma and urine samples, respectively, should be adopted for sublingual administration of detomidine gel.
Objective—To verify the isoflurane anesthetic minimum alveolar concentration (MAC)-sparing effect of a previously administered target plasma fentanyl concentration of 16 ng/mL and characterize an anticipated further sparing in isoflurane MAC associated with higher target plasma fentanyl concentrations.
Procedures—Horses were assigned 2 of 3 target plasma fentanyl concentrations (16, 24, and 32 ng/mL), administered in ascending order. Following determination of baseline MAC, horses received a loading dose of fentanyl followed by a constant rate infusion; MAC determination was performed in triplicate at baseline and at each fentanyl concentration. Venous blood samples were collected throughout the study for determination of actual plasma fentanyl concentrations. Recovery from anesthesia was monitored, and behaviors were rated as excellent, good, fair, or poor.
Results—Mean ± SD fentanyl plasma concentrations were 13.9 ± 2.6 ng/mL, 20.1 ± 3.6 ng/mL, and 24.1 ± 2.4 ng/mL for target concentrations of 16, 24, and 32 ng/mL, respectively. The corresponding changes in the MAC of isoflurane were −3.28%, −6.23%, and +1.14%. None of the changes were significant. Recovery behavior was variable and included highly undesirable, potentially injurious excitatory behavior.
Conclusions and Clinical Relevance—Results of the study did not verify an isoflurane-sparing effect of fentanyl at a plasma target concentration of 16 ng/mL. Furthermore, a reduction in MAC was not detected at higher fentanyl concentrations. Overall, results did not support the routine use of fentanyl as an anesthetic adjuvant in adult horses.
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.
OBJECTIVE To determine effects of 3 plasma concentrations of fentanyl on the minimum alveolar concentration of isoflurane (MACiso) and cardiovascular variables in Hispaniolan Amazon parrots (Amazona ventralis).
ANIMALS 6 adult parrots.
PROCEDURES In phase 1, anesthesia was induced and maintained with isoflurane; intermittent positive-pressure ventilation was provided. The MACiso was determined for each bird by use of a bracketing method and supramaximal electrical stimulus. Fentanyl (20 μg/kg) was administered IV, and blood samples were collected over time to measure plasma fentanyl concentrations for pharmacokinetic calculations. In phase 2, pharmacokinetic values for individual birds were used for administration of fentanyl to achieve target plasma concentrations of 8, 16, and 32 ng/mL. At each concentration, MACiso and cardiovascular variables were determined. Data were analyzed with mixed-effects multilevel linear regression analysis.
RESULTS Mean ± SD fentanyl plasma concentrations were 0 ng/mL, 5.01 ± 1.53 ng/mL, 12.12 ± 3.58 ng/mL, and 24.93 ± 4.13 ng/mL, and MACiso values were 2.09 ± 0.17%, 1.45 ± 0.32%, 1.34 ± 0.31%, and 0.95 ± 0.14% for fentanyl target concentrations of 0, 8, 16, and 32 ng/mL, respectively. Fentanyl significantly decreased MACiso in a dose-dependent manner. Heart rate and blood pressure significantly decreased at all fentanyl doses, compared with values for MACiso at 0 ng of fentanyl/mL.
CONCLUSIONS AND CLINICAL RELEVANCE Fentanyl significantly decreased the MACiso in healthy Hispaniolan Amazon parrots, but this was accompanied by a depressive effect on heart rate and blood pressure that would need to be considered for application of this technique in clinical settings.
OBJECTIVE To compare the disposition of fentanyl citrate after a single IV injection in isoflurane-anesthetized red-tailed hawks (Buteo jamaicensis) and Hispaniolan Amazon parrots (Amazona ventralis).
ANIMALS 6 adult red-tailed hawks and 6 adult Hispaniolan Amazon parrots.
PROCEDURES Anesthesia was induced and maintained with isoflurane; intermittent positive-pressure ventilation was provided. The minimum alveolar concentration of isoflurane was determined for each bird by use of the bracketing method and a supramaximal electrical stimulus. Fentanyl (20 μg/kg) was administered IV. Arterial (red-tailed hawks) or jugular venous (Hispaniolan Amazon parrots) blood samples were obtained immediately before and 1, 2, 4, 8, 15, 30, 60, 120, 180, 240, and 480 minutes (red-tailed hawks) and 1, 5, 10, 15, 30, 60, 120, and 180 minutes (Hispaniolan Amazon parrots) after fentanyl administration.
RESULTS A 3-compartment and a 2-compartment model best described fentanyl pharmacokinetics in red-tailed hawks and Hispaniolan Amazon parrots, respectively. Median apparent volume of the central compartment and volume of distribution at steady state were 222 mL/kg and 987 mL/kg, respectively, for the red-tailed hawks and 5,108 mL/kg and 13,079 mL/kg, respectively, for the Hispaniolan Amazon parrots. Median clearance and elimination half-life were 8.9 mL/min/kg and 90.22 minutes, respectively, for the red-tailed hawks and 198.8 mL/min/kg and 51.18 minutes, respectively, for the Hispaniolan Amazon parrots.
CONCLUSIONS AND CLINICAL RELEVANCE Pharmacokinetic results for fentanyl in isoflurane-anesthetized red-tailed hawks and Hispaniolan Amazon parrots indicated large differences and should strongly discourage extrapolation of doses between these 2 species.