Pharmacokinetics and effects on arachidonic acid metabolism of low doses of cannabidiol following oral administration to horses

التفاصيل البيبلوغرافية
العنوان: Pharmacokinetics and effects on arachidonic acid metabolism of low doses of cannabidiol following oral administration to horses
المؤلفون: Declan Ryan, Heather K Knych, Philip H. Kass, Dan S. McKemie, Birgit Puschner
المصدر: Drug Testing and Analysis. 13:1305-1317
بيانات النشر: Wiley, 2021.
سنة النشر: 2021
مصطلحات موضوعية: Metabolite, Anti-Inflammatory Agents, Administration, Oral, Pharmaceutical Science, Pharmacology, 01 natural sciences, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacokinetics, Tandem Mass Spectrometry, Oral administration, medicine, Animals, Cannabidiol, Environmental Chemistry, Horses, 030216 legal & forensic medicine, Spectroscopy, Inflammation, Arachidonic Acid, Cross-Over Studies, Dose-Response Relationship, Drug, business.industry, 010401 analytical chemistry, Crossover study, 0104 chemical sciences, chemistry, Eicosanoid, business, Biomarkers, Ex vivo, Chromatography, Liquid, Half-Life, medicine.drug, Eicosanoid Production
الوصف: The increasing availability of cannabidiol (CBD) and anecdotal reports of its anti-inflammatory effects has garnered it much interest in the equine industry. The objectives of the current study were to (1) describe the pharmacokinetics of oral CBD in exercising thoroughbreds, (2) characterize select behavioral and physiologic effects, and (3) evaluate effects on biomarkers of inflammation using an ex vivo model. This study was conducted in a randomized balanced 3-way crossover design with a two-week washout period between doses. Horses received a single oral dose (0.5, 1, and 2 mg/kg) of CBD suspended in sesame oil. Blood and urine samples were collected prior to and for 72 hr post drug administration. Additional blood samples collected at select time points were challenged ex vivo with calcium ionophore or lipopolysaccharide to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC-MS/MS. Cannabidiol was well tolerated with no significant behavioral, gastrointestinal, or cardiac abnormalities observed. CBD was readily absorbed, with parent drug detected in blood at all time points. The carboxylated and hydroxylated metabolites predominated in serum and urine, respectively. The terminal half-life for CBD was 10.7 ± 3.61, 10.6 ± 3.84 and 9.88 ± 3.53 for 0.5, 1, and 2 mg/kg. Although the effects were mixed, results of eicosanoid analysis suggest CBD affects COX-1, COX-2 and LOX at the doses studied here. Results of this study coupled with previous reports in other species, suggest further study of CBD in horses is warranted before its use as an anti-inflammatory can be recommended.
تدمد: 1942-7611
1942-7603
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b359184aad6ee67e4b76b14e20e6ea05
https://doi.org/10.1002/dta.3028
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....b359184aad6ee67e4b76b14e20e6ea05
قاعدة البيانات: OpenAIRE