Pharmacokinetics of Buccally Administered Cannabidiol and Oral Carprofen During Single- and Repeated-Dose Administration in Dogs.

Cannabidiol (CBD) is increasingly used as an adjunct treatment for chronic pain in dogs, but information on repeated-dose pharmacokinetics and potential interactions with commonly used analgesics remains limited. This study evaluated the pharmacokinetics of buccally administered CBD, its major metabolites, and orally administered carprofen in dogs, and assessed potential pharmacokinetic changes during co-administration. Twenty-five dogs with osteoarthritis received CBD (2 mg/kg), carprofen (2 mg/kg), or both drugs twice daily for 4 weeks. Plasma samples were collected during the first 12 h after the initial dose and at two and 4 weeks of treatment. Cannabidiol, 7-hydroxy-cannabidiol (7-OH-CBD), 7-carboxy-cannabidiol (7-COOH-CBD), and carprofen concentrations were quantified using LC-MS/MS. Pharmacokinetic parameters were estimated using non-compartmental and compartmental analyses. Cannabidiol was rapidly absorbed but showed substantial interindividual variability. CBD exposure was higher during co-administration with carprofen, but differences in Cmax and AUClast were not significant. Repeated dosing resulted in increasing 2-h post-dose CBD concentrations over time. Among metabolites, 7-COOH-CBD showed greater exposure and persistence than 7-OH-CBD. Carprofen pharmacokinetics were consistent with previous reports, with higher but non-significant Cmax and AUClast during co-administration with CBD. These findings warrant further investigation of potential pharmacokinetic interactions between CBD and carprofen.