Describe the pharmacokinetics of grapiprant administered orally with food to red-tailed hawks (RTHAs; Buteo jamaicensis) and compare the results with previously described grapiprant pharmacokinetics administered without food in this species.
6 healthy adult RTHA (3 males, 3 females) under human care.
A single dose of grapiprant (30 mg/kg) was given orally to RTHAs, followed by force-feeding. Blood samples were obtained at 14 time points for 120 hours postgrapiprant administration. Plasma concentrations of grapiprant were measured via tandem liquid chromatography-mass spectrometry. Nonparametric superimposition using pharmacokinetic modeling software used plasma concentrations to calculate simulations of grapiprant plasma concentrations for 30 mg/kg administered orally with food every 12 hours.
The arithmetic mean maximum plasma concentration was 405.8 ng/mL, time to maximum plasma concentration was 16 hours, and harmonic mean terminal half-life was 15.6 hours. Simulations determined 30 mg/kg every 12 hours could attain minimum effective concentrations (> 164 ng/mL) reported in dogs for a sustained period of approximately 20 hours.
Grapiprant plasma concentrations were achieved above the canine therapeutic concentrations within 16 hours postmedication. Mean concentrations were maintained for approximately 20 hours. Simulations support a dosing frequency of 12-hour intervals with food reaching minimum effective concentrations established for canines, although it is unknown whether these plasma concentrations are therapeutic for birds. Bioaccumulation was not noted on simulations secondary to increased grapiprant administration. Further research including multidose assessments at this current dose with food, in vitro pharmacological characterization, and pharmacodynamic studies in this species are warranted.
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.
To evaluate a carrageenan-induced inflammatory model in the cockatiel (Nymphicus hollandicus) using weight-bearing load, rotational perch locomotion, thermal threshold withdrawal, and footpad dimensions.
16 adult cockatiels (8 males and 8 females).
Cockatiels were randomly assigned into 2 groups as either treatment (carrageenan injection; n = 8) or control (handling only; 8). Treatment of cockatiels involved unilateral subcutaneous injection of 0.05 mL of 1% lambda carrageenan solution into the left footpad. Control birds were handled in a similar manner without an injection. Following baseline measurements and treatment or control procedures, posttreatment measurements at multiple time points involving weight-bearing perch load (for up to 336 hours), locomotive abilities when placed on a rotating perch (for up to 96 hours), thermal withdrawal threshold (for the 24- to 30-hour period), and both vertical and horizontal left footpad size and degree of swelling (for up to 84 days) were obtained.
Treatment cockatiels had a significant decrease in left foot weight-bearing load and increase in left footpad dimensions and swelling grade over time compared to control cockatiels. Rotational perch locomotion and thermal withdrawal threshold, conversely, did not differ significantly between groups. Cockatiels injected with carrageenan returned to normal weight-bearing within 2 weeks; however, left footpad dimensions did not return to baseline.
Carrageenan footpad injection prompts a measurable and grossly visible inflammatory response in the cockatiel. Additionally, it induces alterations in weight-bearing distribution in injected birds. This model provides a method to evaluate inflammation and lameness in small psittacine species.