Feeding decreases the oral bioavailability of cannabidiol and cannabidiolic acid in hemp oil in New Zealand White rabbits (Oryctolagus cuniculus)

TA Rooney, JW Carpenter, B KuKanich… - American journal of …, 2022 - Am Vet Med Assoc
TA Rooney, JW Carpenter, B KuKanich, SM Gardhouse, GC Magnin, TN Tully
American journal of veterinary research, 2022Am Vet Med Assoc
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 …
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 (C max ) was 30.4 and 15 ng/mL, the time to C max (t max ) was 3.78 and 3.25 hours, and the terminal half-life (t 1/2λ ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively. For CBDA, the AUC 0–∞ was 12,286 and 6,176 hours X ng/mL, C max was 2,573 and 1,196 ng/mL, t max was 1.07 and 1.12 hours, and t 1/2λ 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 C max and had a longer t 1/2λ in phase 1 (without food) compared with phase 2 (with food). CBDA reached a greater C max but had a shorter t 1/2λ than CBD both in phase 1 and phase 2. These data may be useful in determining appropriate dosing of cannabinoids in the domestic rabbit.
Am Vet Med Assoc
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