Osteoarthritis is anecdotally considered one of the most common causes of chronic pain in birds.1 The prevalence of osteoarthritis in nonpasserine birds was estimated to be as high as 20% in a study2 of cadaveric bird skeletons, but epidemiologic research into osteoarthritis in companion parrots is lacking, and therefore, the prevalence may be higher. Long-term pain management is needed for parrots with osteoarthritis because parrots have a long life expectancy.1 Medical management of osteoarthritis includes administration of opioids, NSAIDs, polysulfated glycosaminoglycans, glucosamine, chondroitin, derivatives of γ-aminobutyric acid (eg, gabapentin and pregabalin), and amantadine.3,4
Amantadine increases the release of dopamine in the CNS, and via weak antagonism of N-methyl-d-aspartic acid receptors, it decreases tolerance to opioid medications.3,4 Administration of this drug is expected to reduce nociception associated with chronic pain, in which sensory neurons are hypersensitive to noxious stimuli and responsive to non-noxious stimuli (ie, central sensitization).4 Amantadine can be used alone for analgesia, but its weak affinity for N-methyl-d-aspartic acid receptors may necessitate multimodal treatments to effectively manage pain in veterinary patients.4,5 Amantadine is synergistic with NSAIDs, opioids, and derivatives of γ-aminobutyric acid.4 In humans, amantadine has been shown to decrease opioid use by patients after surgery, decrease pain in those with postherpetic neuralgia, and aid in neuropathic analgesia.6,7 Oral administration of amantadine at 3 to 5 mg/kg every 24 hours in conjunction with meloxicam significantly improved owner-assessed activity as rated with a Likert scale of dogs with osteoarthritis, compared with meloxicam alone.8 Through amantadine's unique mechanisms of action, it may provide analgesia in parrots with pain that is refractory to treatment with other drugs, and thus may be considered an adjunct for ameliorating chronic pain.
Information on the pharmacokinetics and pharmacodynamics of amantadine in birds is lacking, and knowledge of both is important to ensure appropriate dosing. Furthermore, knowledge of the adverse effects of amantadine after administration of a single dose and multiple doses is necessary if amantadine is to be used to treat chronic pain in birds.
The purpose of the study reported here was to determine the pharmacokinetics of amantadine after oral administration of a single dose and of multiple doses to orange-winged Amazon parrots (Amazona amazonica). We hypothesized that amantadine administered orally at a dosage of 5 to 20 mg/kg every 24 hours would yield plasma concentrations considered to be therapeutic in dogs with minimal adverse effects in parrots.8,9
Funded by the Richard M. Schubot Parrot Wellness and Welfare Program at the Center for Companion Animal Health, School of Veterinary Medicine, University of California-Davis.
The authors declare that there were no conflicts of interest.
Presented in abstract form at the Annual Conference of the Association of Avian Veterinarians, St Louis, September 2019.
Area under the concentration-versus-time curve
Maximum plasma concentration
Time to maximum plasma concentration
Roudybush Daily Maintenance, Roudybush Inc, Woodland, Calif.
Phoenix Winnonlin, version 8.2, Certara, Princeton, NJ.
Microtainer, Becton, Dickinson and Co, Franklin Lakes, NJ.
Bio Plas Inc, San Rafael, Calif.
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