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Abstract

OBJECTIVE

To examine the pharmacokinetics and ex vivo pharmacodynamics of oral firocoxib administration in New Zealand White rabbits (Oryctolagus cuniculus).

ANIMALS

6 healthy New Zealand White rabbits.

PROCEDURES

Pharmacokinetics were determined from plasma concentrations measured via ultra performance liquid chromatography-tandem mass spectrometry after oral administration of firocoxib at a dose of 3.74 to 4.20 mg/kg. Pharmacokinetic analysis was performed using non compartmental methods. Pharmacodynamics of firocoxib were evaluated by measuring plasma concentrations of thromboxane and prostaglandin via ELISAs as surrogate markers of cyclooxygenase enzyme isoform inhibition.

RESULTS

The terminal rate constant was 0.07 hours (range, 0.05 to 0.11 h). The mean maximum concentration (Cmax) and time to Cmax were 0.16 µg/mL and 3.81 hours (range, 2.0 to 8.0 h), respectively. Mean residence time was 15.02 hours. Mean elimination half-life was 9.12 hours. For the pharmacodynamic analysis, firocoxib administration did not demonstrate a significant difference between any time point for prostaglandin E2 and only a significant difference between 24 and 48 hours for thromboxane B2.

CLINICAL RELEVANCE

Although the pharmacokinetic research supports that plasma firocoxib concentrations that would be therapeutic in dogs are achieved in rabbits, the pharmacodynamic results do not demonstrate a significant difference in levels of cyclooxygenase-2 inhibition, which indirectly reflects the anti-inflammatory effects of the drug. Further pharmacodynamic studies and multidose studies are warranted to determine the efficacy and safety of this drug in rabbits.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the pharmacokinetics of a solution containing cannabidiol (CBD) and cannabidiolic acid (CBDA), administered orally in 2 single-dose studies (with and without food), in the domestic rabbit (Oryctolagus cuniculus).

ANIMALS

6 healthy New Zealand White rabbits.

PROCEDURES

In phase 1, 6 rabbits were administered 15 mg/kg CBD with 16.4 mg/kg CBDA orally in hemp oil. In phase 2, 6 rabbits were administered the same dose orally in hemp oil followed by a food slurry. Blood samples were collected for 24 hours to determine the pharmacokinetics of CBD and CBDA. Quantification of plasma CBD and CBDA concentrations was determined using a validated liquid chromatography–mass spectrometry (LC-MS) assay. Pharmacokinetics were determined using noncompartmental analysis.

RESULTS

For CBD, the area under the curve extrapolated to infinity (AUC)0–∞ was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (Cmax) was 30.4 and 15 ng/mL, the time to Cmax (tmax) was 3.78 and 3.25 hours, and the terminal half-life (t1/2λ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively. For CBDA, the AUC0–∞ was 12,286 and 6,176 hours X ng/mL, Cmax was 2,573 and 1,196 ng/mL, tmax was 1.07 and 1.12 hours, and t1/2λ was 3.26 and 3.49 hours in phase 1 and phase 2, respectively. Adverse effects were not observed in any rabbit.

CLINICAL RELEVANCE

CBD and CBDA reached a greater Cmax and had a longer t1/2λ in phase 1 (without food) compared with phase 2 (with food). CBDA reached a greater Cmax but had a shorter t1/2λ than CBD both in phase 1 and phase 2. These data may be useful in determining appropriate dosing of cannabinoids in the domestic rabbit.

Open access
in American Journal of Veterinary Research