To identify an oral dose of grapiprant for red-tailed hawks (RTHAs; Buteo jamaicensis) that would achieve a plasma concentration > 164 ng/mL, which is considered therapeutic for dogs with osteoarthritis.
6 healthy adult RTHAs.
A preliminary study, in which grapiprant (4 mg/kg [n = 2], 11 mg/kg , or 45 mg/kg ) was delivered into the crop of RTHAs from which food had been withheld for 24 hours, was performed to obtained pharmacokinetic data for use with modeling software to simulate results for grapiprant doses of 20, 25, 30, 35, and 40 mg/kg. Simulation results directed our selection of the grapiprant dose administered to the RTHAs in a single-dose study. Plasma grapiprant concentration, body weight, and gastrointestinal signs of RTHAs were monitored.
On the basis of results from the preliminary study and simulations, a grapiprant dose of 30 mg/kg was used in the single-dose study. The geometric mean maximum observed plasma concentration of grapiprant was 3,184 ng/mL, time to maximum plasma grapiprant concentration was 2.0 hours, and the harmonic mean terminal half-life was 17.1 hours. No substantial adverse effects were observed.
CONCLUSIONS AND CLINICAL RELEVANCE
Although the single dose of grapiprant (30 mg/kg) delivered into the crop achieved plasma concentrations > 164 ng/mL in the RTHAs, it was unknown whether this concentration would be therapeutic for birds. Further research that incorporates multidose assessments, safety monitoring, and pharmacodynamic data collection is warranted on the use of grapiprant in RTHAs from which food was withheld versus not withheld.
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.
OBJECTIVE To compare analgesic and gastrointestinal effects of lidocaine and buprenorphine administered to rabbits undergoing ovariohysterectomy.
ANIMALS Fourteen 12-month-old female New Zealand White rabbits.
PROCEDURES Rabbits were assigned to 2 treatment groups (7 rabbits/group). One group received buprenorphine (0.06 mg/kg, IV, q 8 h for 2 days), and the other received lidocaine (continuous rate infusion [CRI] at 100 μg/kg/min for 2 days). Variables, including food and water consumption, fecal output, glucose and cortisol concentrations, and behaviors while in exercise pens, were recorded.
RESULTS Rabbits receiving a lidocaine CRI had significantly higher gastrointestinal motility, food intake, and fecal output and significantly lower glucose concentrations, compared with results for rabbits receiving buprenorphine. Rabbits receiving lidocaine also had a higher number of normal behaviors (eg, sprawling, traveling, and frolicking) after surgery, compared with behaviors such as crouching and sitting that were seen more commonly in rabbits receiving buprenorphine. Both groups had significant weight loss after surgery. Pain scores did not differ significantly between treatment groups. Significant decreases in heart rate and respiratory rate were observed on the day of surgery, compared with values before and after surgery. Rabbits in the lidocaine group had significantly overall lower heart rates than did rabbits in the buprenorphine group.
CONCLUSIONS AND CLINICAL RELEVANCE A CRI of lidocaine to rabbits provided better postoperative outcomes with respect to fecal output, food intake, and glucose concentrations. Thus, lidocaine appeared to be a suitable alternative to buprenorphine for alleviating postoperative pain with minimal risk of anorexia and gastrointestinal ileus.