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

Vake T.; Tomsič K.; Žgank &.; Klasić M.; Babič J.; Bajc Z.; Dolenc J.; Kalcher G.; Planinšek O.; Snoj T. · Journal of veterinary pharmacology and therapeutics · 2026

**Background & Methods** This pharmacokinetic study evaluated 25 dogs with osteoarthritis receiving buccal cannabidiol (CBD), oral carprofen, or both agents twice daily for 4 weeks. Plasma samples were collected at 12 hours post-initial dose and at 2 and 4 weeks of treatment, with drug concentrations quantified using LC-MS/MS and analyzed via non-compartmental and compartmental methods. **Key Findings** • CBD demonstrated rapid buccal absorption with substantial interindividual variability; repeated dosing resulted in increasing 2-hour post-dose CBD concentrations over the 4-week treatment period, suggesting potential accumulation with chronic administration. • Co-administration with carprofen resulted in higher CBD exposure (increased Cmax and AUClast), though differences were not statistically significant; carprofen pharmacokinetics remained consistent with previous reports and were minimally affected by CBD co-treatment. • Among CBD metabolites, 7-carboxy-cannabidiol (7-COOH-CBD) demonstrated greater exposure and longer persistence compared to 7-hydroxy-cannabidiol (7-OH-CBD), indicating differential metabolite accumulation during repeated dosing. **Dosage & Administration** Cannabidiol: 2 mg/kg buccally, twice daily for 4 weeks. Carprofen: 2 mg/kg orally, twice daily for 4 weeks. **Safety & Adverse Effects** Not reported. **Evidence Quality** This study represents original research on repeated-dose CBD pharmacokinetics in a veterinary population, addressing a clinically relevant gap regarding drug-drug interactions. However, several limitations warrant consideration: the small sample size (25 dogs) limits generalizability; lack of adverse event monitoring prevents safety characterization; the relatively short 4-week treatment duration may not capture long-term accumulation patterns; and the non-significant findings for potential CBD-carprofen interactions require larger, adequately powered studies for definitive conclusions. The substantial interindividual variability in CBD absorption necessitates further investigation into factors affecting bioavailability. This represents moderate-quality evidence providing preliminary data on CBD pharmacokinetics in dogs with chronic pain, establishing rationale for larger-scale, controlled trials examining safety profiles and clinical efficacy of CBD-NSAID combinations in veterinary medicine.

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