Abstract

Pain management is an essential part of both post-surgical recovery and treatment of chronic disease for animals. Pain control improves recovery rates and survival times of humans and laboratory animals.^1,2 Birds, especially parrots, are common companion animals and appropriate analgesia is a critical part of veterinary care for these species. Several recent advances in the study of avian analgesia validate the clinical use of analgesic drugs for the psittacine patient.^3-7 However, there are still significant barriers to providing adequate pain relief for birds, including frequent dosing schedules and the associated stress of frequent injections. Opioids are the most effective class of analgesic drugs for post-operative pain. Reliable techniques have been developed to evaluate the efficacy of analgesic drugs in birds including isoflurane-sparing techniques and antinociceptive testing methods.^4-8,11 Opioid drugs with different receptor affinities have been evaluated in psittacines and pigeons, including butorphanol (mixed agonist/antagonist with kappa agonist activity), buprenorphine (mixed agonist/antagonist with mu agonist activity), and fentanyl (mu agonist).^4-8 Based on these studies, the order of analgesic effectiveness in psittacines is 2 mg/kg butorphanol (most effective), 0.1 mg/kg buprenorphine and 0.02 mg/kg fentanyl (least effective).^4-8 The results of pharmacokinetic studies using these opioids in psittacines indicate that 2 mg/kg IM butorphanol, 0.02 mg/kg IM fentanyl and 0.1 mg/kg IM buprenorphine have very short mean residence times (MRT) of 1.13 (±0.46), 1.98(±0.22) and 1.05 (±0.14) hours respectively.^8-10 Therefore, butorphanol is an effective analgesic for birds, but its clinical usefulness is limited by a very short half-life.

Encapsulation into liposomes is one method of preparing long-acting formulations of opioid drugs.^12-15 LE-morphine administered to mice produces significant plasma concentrations for 6 days after a single SC injection, and both LE-morphine and LE-oxymorphone administered to rats provided effective analgesia for 7 days following a single SC injection.^12,14 However, these products will not be optimal for use in avian patients because morphine is a poor analgesic for birds. Encapsulating butorphanol into liposomes would be an efficacious preparation for use in avian and laboratory species.

This study was undertaken to evaluate the analgesic efficacy and pharmacodynamics of a clinically relevant liposome encapsulated butorphanol tartrateformulation (LEBT) in the Hispaniolan parrot (Amazona ventralis). An ELISA method was used to detect butorphanol and its metabolites in parrot serum. Following a single IM dose of standard butorphanol tartate (2 mg/kg IM; n=4), serum concentrations of butorphanol peaked at approximately 1 hour and were rapidly cleared. In contrast, following a single dose of LEBT (15 mg/kg; n=10) or 10 mg/kg n=4), serum concentrations of butorphanol were elevated for 5 and 8 days respectively. No detrimental side effects were observed in any bird subject.

Analgesimetry data were collected using both thermal and electrical noxious stimuli delivered to the plantar surface of the foot. Latency to foot withdrawal was measured using a modified perch design. Compared to controls receiving liposomes without butorphanol (LE), administration of a single dose of LEBT (15 mg/kg SC) maintained an increased threshold to the noxious stimulus for 3 days based on thermal thresholds and 6 days based on electrical thresholds. There were no significant changes in foot withdrawal latencies after administration of LE alone. These data suggest that liposome-encapsulated butorphanol administered at 15 mg/kg SC is analgesic for 3–5 days after a single dose.

Literature Cited

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