Evaluation of the thermal antinociceptive effects and pharmacokinetics of hydromorphone hydrochloride after intramuscular administration to cockatiels (Nymphicus hollandicus)

Abstract

OBJECTIVE To evaluate the thermal antinociceptive effects and pharmacokinetics of hydromorphone hydrochloride after IM administration to cockatiels (Nymphicus hollandicus). ANIMALS 16 healthy adult cockatiels. PROCEDURES During the first of 2 study phases, each cockatiel received each of 4 treatments (hydromorphone at doses of 0.1, 0.3, and 0.6 mg/kg and saline [0.9% NaCl] solution [0.33 mL/kg; control], IM), with a 14-day interval between treatments. For each bird, foot withdrawal to a thermal stimulus was determined following assignment of an agitation-sedation score at predetermined times before and for 6 hours after each treatment. During the second phase, a subset of 12 birds received hydromorphone (0.6 mg/kg, IM), and blood samples were collected at predetermined times for 9 hours after drug administration. Plasma hydromorphone concentration was determined by liquid chromatography-mass spectrometry. Noncompartmental analysis of sparse data was used to calculate pharmacokinetic parameters. RESULTS Thermal withdrawal response did not differ among the 4 treatment groups at any time. Agitation-sedation scores following administration of the 0.3-and 0.6-mg/kg doses of hydromorphone differed significantly from those treated with saline solution and suggested the drug had a sedative effect. Plasma hydromorphone concentrations were > 1 ng/mL for 3 to 6 hours after drug administration in all birds. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IM administration of hydromorphone at the evaluated doses did not increase the thermal withdrawal threshold of cockatiels despite plasma drug concentrations considered therapeutic for other species. Further research is necessary to evaluate the analgesic effects of hydromorphone in cockatiels.

Varying Expression of Mu and Kappa Opioid Receptors in Cockatiels (Nymphicus hollandicus) and Domestic Pigeons (Columba livia domestica)

“…Similar to humans, both the cockatiel and pigeon tissues in this study had relatively lower OPRK1 expression levels compared to OPRM1 in all tissues with expression data (Peng et al, 2012). However, the findings documenting the level of expression for each type of receptor were somewhat unexpected when considering clinical experience and the previous antinociception studies in cockatiels (Guzman et al, 2018;Houck et al, 2018). Kappa agonistic drugs are the current recommendation for cockatiels based on studies in other psittacine species (Paul-Murphy et al, 1999, 2009aSladky et al, 2006); however, there was less OPRK1 in the cerebrum compared to pigeons and less OPRK1 compared to OPRM1 in cockatiel tissues overall.…”

“…Interestingly, there was decreased OPRM1 expression in cockatiel footpad compared to pigeon footpad which supports a possible explanation for the lack of analgesic effect in cockatiels receiving mu-agonists during thermal foot withdrawal antinociceptive studies (Guzman et al, 2018;Houck et al, 2018). A large limitation of this study is a potential lack of power due to the small number of animals utilized.…”

“…The analgesic effects of opioids have a wide range of clinical efficacy depending on the avian species studied. For example, in cockatiels, mu agonists such as buprenorphine or hydromorphone did not yield a significant thermal antinociceptive effect when delivered intramuscularly (Guzman et al, 2018;Houck et al, 2018). However, similar doses of hydromorphone that were not effective in cockatiels induced thermal antinociception in another avian species, American kestrels (Guzman et al, 2013).…”

A Critical Review of the Pharmacokinetics and Pharmacodynamics of Opioid Medications Used in Avian Patients

“…Hydromorphone, also known as dihydromorphinone, is a semi-synthetic µ-opioid receptor agonist, which also displays weak affinity for κ-opioid receptors [67]. The use of hydromorphone has been examined in several avian species including American Kestrel (Falco sparverius) [35,36], Cockatiel (Nymphicus hollandicus) [37] and Orange-winged Amazon (Amazona amazonica) [38,39].…”

“…Generally, plasma concentrations of all species studied reached or exceeded plasma concentrations associated with analgesia in American Kestrel, with duration ranging from 3 to 6 h. PD studies conducted in American Kestrel [35,36] and Orange-winged Amazon [38,39] showed the effectiveness of hydromorphone in providing an analgesic effect to thermal stimuli at the given plasma concentration. One exception, however, is that of cockatiel [37]. Despite reaching plasma concentrations associated with analgesia in American kestrel, there is no significant increase in the thermal withdrawal threshold in cockatiel receiving 0.6 mg/kg hydromorphone [37].…”