Pharmacology and antinociception of a sustained-released butorphanol – poloxamer 407 formulation in Amazon parrots

Abstract

Butorphanol is an opioid drug used for pain management in Psittacidae. It has a short duration of action (2-3h) when administered IM or IV. In order to decrease frequency of handling and injections, there is a need for a long-acting opioid analgesic in avian medicine. Poloxamer 407 (P407) is a hydrogel commonly used to prepare sustained-release drugs. P407 is liquid when cold and becomes a gel at body temperature. The objective of this study was to evaluate the rheological properties and in vitro diffusion of a formulation of butorphanol in a P407 base (But-P407), as well as its pharmacokinetic parameters and nociceptive effects in Amazon parrots. But-P407 25% (8.3 mg/mL) had in vitro characteristics that made it a good candidate for a sustained-release analgesic medication: it was a gel at avian body temperature, could be sterilized by microfiltration, and its diffusion through a dialysis membrane was slower than that of butorphanol tartrate. Butorphanol was well absorbed from But-P407 25% in Hispaniolan Amazon parrots (Amazona ventralis) (12.5 mg/kg SC), and its pharmacokinetic profile was compatible with a sustained-release drug. Plasma concentrations stayed above the suspected therapeutic threshold for 3-8h. However, no analgesic effect of this formulation could be detected in orange-winged Amazon parrots (Amazona amazonica) (12.5 mg/kg SC) delivered a thermal noxious stimulus. These results could reflect poor analgesic effect of butorphanol, confounding of the poloxamer base, or a lack of sensitivity of the thermal analgesiometric model in this species. Further studies are warranted to provide recommendations for the clinical use of But-P407 25% in birds.