To evaluate the thermal antinociceptive effects of hydromorphone hydrochloride after IM administration to orange-winged Amazon parrots (Amazona amazonica).
8 healthy adult parrots (4 males and 4 females).
In a randomized crossover study, each bird received hydromorphone (0.1, 1, and 2 mg/kg) and saline (0.9% NaCl) solution (1 mL/kg; control) IM, with a 7-day interval between treatments. Each bird was assigned an agitation-sedation score, and the thermal foot withdrawal threshold (TFWT) was measured at predetermined times before and after treatment administration. Adverse effects were also monitored. The TFWT, agitation-sedation score, and proportion of birds that developed adverse effects were compared among treatments over time.
Compared with the mean TFWT for the control treatment, the mean TFWT was significantly increased at 0.5, 1.5, and 3 hours and 1.5, 3, and 6 hours after administration of the 1- and 2-mg/kg hydromorphone doses, respectively. Significant agitation was observed at 0.5, 1.5, and 3 hours after administration of the 1 - and 2-mg/kg hydromorphone doses. Other adverse effects observed after administration of the 1- and 2-mg/kg doses included miosis, ataxia, and nausea-like behavior (opening the beak and moving the tongue back and forth).
CONCLUSIONS AND CLINICAL RELEVANCE
Although the 1- and 2-mg/kg hydromorphone doses appeared to have antinociceptive effects, they also caused agitation, signs of nausea, and ataxia. Further research is necessary to evaluate administration of lower doses of hydromorphone and other types of stimulation to better elucidate the analgesic and adverse effects of the drug in psittacine species.
First, butorphanol tartrate (5 mg/kg) or saline (0.9% NaCl) solution was administered IM to birds in a randomized complete crossover design. The temperature prompting a foot withdrawal response to a thermal stimulus (ie, the thermal threshold) was determined 30 minutes before (baseline) and at various points after treatment administration. Second, But-P407 (12.5 mg/kg) or P407 was administered SC in a similar crossover design. Thermal threshold was determined before and at various points after treatment administration. Third, But-P407 (12.5 mg/kg) or saline solution was administered SC and evaluated as in the second trial. Sedation was scored immediately before each time point in all 3 trials.
In the first trial, a significant increase in thermal threshold was noted 30 minutes after butorphanol tartrate (vs saline solution) administration. No sedation was noted. In the second and third trials, no significant difference was identified between results for But-P407 and those for either control treatment (saline solution or P407). Mild sedation was noted in the second trial following But-P407 administration.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested a small but significant thermal antinociceptive effect of butorphanol tartrate lasting between 30 minutes and 1.5 hours in orange-winged Amazon parrots. No antinociceptive effect of butorphanol tartrate was demonstrated when delivered in P407. Further research is needed to evaluate the potential analgesic effects of But-P407.
To determine the pharmacokinetics of butorphanol tartrate incorporated into poloxamer 407 (P407) after subcutaneous administration to orange-winged Amazon parrots (Amazona amazonica).
Six orange-winged Amazon parrots, ages 28 to 45 years.
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.
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.
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.