Publikationsdatenbank

Pharmacokinetic modeling of orally administered cannabidiol and implications for medication control in horses (2023)

Art

Vortrag

Autoren

Eichler, F. (WE 17)

Poźniak, B.

Machnik, M.

Schenk, I.

Wingender, A.

Baudisch, N. (WE 17)

Thevis, M.

Bäumer, W. (WE 14)

Lischer, C. (WE 17)

Ehrle, A. (WE 17)

Kongress

15th International Congress of the European Association for Veterinary Pharmacology and Toxicology

Bruges, Belgium, 02. – 05.07.2023

Quelle

Journal of veterinary pharmacology and therapeutics

Bandzählung: 46

Heftzählung: S1

Seiten: 57 – 58

ISSN: 1365-2885

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/10.1111/jvp.13227

DOI: 10.1111/jvp.13227

Kontakt

Pferdeklinik

Oertzenweg 19 b
14163 Berlin
+49 30 838 62299 / 62300
pferdeklinik@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Introduction:
Cannabidiol (CBD) products gain increasing popularity among animal owners and veterinarians as an alternative remedy for treatment of stress, inflammation or pain in horses. Whilst the use of cannabinoids is banned in equestrian sports, there is limited information available concerning CBD detection times in blood or urine. The aim of this study was to determine the pharmacokinetic properties of CBD following oral administration in the horse to assist doping control laboratories and equestrian sport authorities with interpreting analytical results for CBD.

Materials and Methods:
Part 1 - dose escalation study: Single oral administration of three escalating doses of CBD paste (0.2 mg/kg, n = 3 horses; 1 mg/kg, n = 3; 3 mg/kg, n = 5) with >7 days wash-out periods in between. Part 2 - multiple dose study: oral administration of CBD paste (3 mg/kg, n = 6) twice daily for 15 days. Multiple blood and urine samples were collected daily throughout both studies. Following study part 2, blood and urine samples were collected for 14 days to observe the elimination phase. Concentrations of CBD, its metabolites (7-carboxy-CBD and 7-hydroxy-CBD) and further cannabinoids were evaluated using gas-chromatography/tandem-mass-spectrometry. Pharmacokinetic parameters were assessed via two approaches: population pharmacokinetic analysis using nonlinear mixed-effects modeling and non-compartmental analysis. AUC0–12h and Cmax were tested for dose proportionality using a power model approach. During the elimination phase, the CBD steady-state urine to serum concentration ratio (Rss) was calculated.

Results:
Oral CBD medication was well-tolerated in horses. Based on population pharmacokinetics, a 3-compartment-model with zero-order absorption most accurately describes the pharmacokinetic properties of CBD. High volumes of distribution into peripheral compartments and high concentrations of 7-carboxy-CBD were observed in serum. Non-compartmental analysis identified a Cmax of 12.17 ± 2.08 ng/mL and AUC0–12h of 59.53 ± 13.54 h·ng/ml after single administration of CBD (dose: 3 mg/kg). AUC0–12h showed dose proportionality, Cmax showed a decline at higher doses. AUC0–12h for 7-carboxy-CBD was 1768.38 ± 450.86 h·ng/ml. Following multiple doses, the CBD terminal half-life was 161.29 ± 43.65 h in serum. Rss was 4.45 ± 1.04.

Conclusions:
CBD is extensively metabolized and shows high volumes of tissue distribution with a resulting extended elimination phase. Further investigation of the potential calming and anti-inflammatory effects of CBD are required to determine cut-off values for medication control using the calculated Rss.