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Pharmacokinetics of cannabidiol following intranasal, intrarectal, and oral administration in healthy dogs

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Abstract
The therapeutic potential of cannabidiol (CBD), a non-psychtropic component of the Cannabis sativa plant, is substantiated more and more. We aimed to determine the pharmacokinetic behavior of CBD after a single dose via intranasal (IN) and intrarectal (IR) administration in six healthy Beagle dogs age 3-8 years old, and compare to the oral administration route (PO). Standardized dosages applied for IN, IR and PO were 20, 100, and 100 mg, respectively. Each dog underwent the same protocol but received CBD through a different administration route. CBD plasma concentrations were determined by ultra-high performance liquid chromatography-tandem mass spectrometry before and at fixed time points after administration. Non-compartmental analysis was performed on the plasma concentration-time profiles. Plasma CBD concentrations after IR administration were below the limit of quantification. The mean area under the curve (AUC) after IN and PO CBD administration was 61 and 1,376 ng/mL*h, respectively. The maximal plasma CBD concentration (C-max) after IN and PO CBD administration was 28 and 217 ng/mL reached after 0.5 and 3.5 h (T-max), respectively. Significant differences between IN and PO administration were found in the T-max (p = 0.04). Higher AUC and C-max were achieved with 100 mg PO compared to 20 mg IN, but no significant differences were found when AUC (p = 0.09) and C-max (p = 0.44) were normalized to 1 mg dosages. IN administration of CBD resulted in faster absorption when compared to PO administration. However, PO remains the most favorable route for CBD delivery due to its more feasible administration. The IR administration route is not advised for clinical application.
Keywords
Canine, cannabinoid, Cannabis sativa, phytocannabinoid, tetrahydrocannabinol, SEIZURE FREQUENCY, MEDICAL CANNABIS, IN-VIVO, EPILEPSY, NASAL, DELIVERY, BIOAVAILABILITY, FORMULATIONS, TOXICITY, DIAZEPAM

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MLA
Polidoro, Dakir, et al. “Pharmacokinetics of Cannabidiol Following Intranasal, Intrarectal, and Oral Administration in Healthy Dogs.” FRONTIERS IN VETERINARY SCIENCE, vol. 9, 2022, doi:10.3389/fvets.2022.899940.
APA
Polidoro, D., Temmerman, R., Devreese, M., Charalambous, M., Van Ham, L., Cornelis, I., … Bhatti, S. (2022). Pharmacokinetics of cannabidiol following intranasal, intrarectal, and oral administration in healthy dogs. FRONTIERS IN VETERINARY SCIENCE, 9. https://doi.org/10.3389/fvets.2022.899940
Chicago author-date
Polidoro, Dakir, Robin Temmerman, Mathias Devreese, Marios Charalambous, Luc Van Ham, Ine Cornelis, Bart Broeckx, et al. 2022. “Pharmacokinetics of Cannabidiol Following Intranasal, Intrarectal, and Oral Administration in Healthy Dogs.” FRONTIERS IN VETERINARY SCIENCE 9. https://doi.org/10.3389/fvets.2022.899940.
Chicago author-date (all authors)
Polidoro, Dakir, Robin Temmerman, Mathias Devreese, Marios Charalambous, Luc Van Ham, Ine Cornelis, Bart Broeckx, Paul J. J. Mandigers, Fischer Andrea, Jan Storch, and Sofie Bhatti. 2022. “Pharmacokinetics of Cannabidiol Following Intranasal, Intrarectal, and Oral Administration in Healthy Dogs.” FRONTIERS IN VETERINARY SCIENCE 9. doi:10.3389/fvets.2022.899940.
Vancouver
1.
Polidoro D, Temmerman R, Devreese M, Charalambous M, Van Ham L, Cornelis I, et al. Pharmacokinetics of cannabidiol following intranasal, intrarectal, and oral administration in healthy dogs. FRONTIERS IN VETERINARY SCIENCE. 2022;9.
IEEE
[1]
D. Polidoro et al., “Pharmacokinetics of cannabidiol following intranasal, intrarectal, and oral administration in healthy dogs,” FRONTIERS IN VETERINARY SCIENCE, vol. 9, 2022.
@article{8755644,
  abstract     = {{The therapeutic potential of cannabidiol (CBD), a non-psychtropic component of the Cannabis sativa plant, is substantiated more and more. We aimed to determine the pharmacokinetic behavior of CBD after a single dose via intranasal (IN) and intrarectal (IR) administration in six healthy Beagle dogs age 3-8 years old, and compare to the oral administration route (PO). Standardized dosages applied for IN, IR and PO were 20, 100, and 100 mg, respectively. Each dog underwent the same protocol but received CBD through a different administration route. CBD plasma concentrations were determined by ultra-high performance liquid chromatography-tandem mass spectrometry before and at fixed time points after administration. Non-compartmental analysis was performed on the plasma concentration-time profiles. Plasma CBD concentrations after IR administration were below the limit of quantification. The mean area under the curve (AUC) after IN and PO CBD administration was 61 and 1,376 ng/mL*h, respectively. The maximal plasma CBD concentration (C-max) after IN and PO CBD administration was 28 and 217 ng/mL reached after 0.5 and 3.5 h (T-max), respectively. Significant differences between IN and PO administration were found in the T-max (p = 0.04). Higher AUC and C-max were achieved with 100 mg PO compared to 20 mg IN, but no significant differences were found when AUC (p = 0.09) and C-max (p = 0.44) were normalized to 1 mg dosages. IN administration of CBD resulted in faster absorption when compared to PO administration. However, PO remains the most favorable route for CBD delivery due to its more feasible administration. The IR administration route is not advised for clinical application.}},
  articleno    = {{899940}},
  author       = {{Polidoro, Dakir and Temmerman, Robin and Devreese, Mathias and Charalambous, Marios and Van Ham, Luc and Cornelis, Ine and Broeckx, Bart and Mandigers, Paul J. J. and Andrea, Fischer and Storch, Jan and Bhatti, Sofie}},
  issn         = {{2297-1769}},
  journal      = {{FRONTIERS IN VETERINARY SCIENCE}},
  keywords     = {{Canine,cannabinoid,Cannabis sativa,phytocannabinoid,tetrahydrocannabinol,SEIZURE FREQUENCY,MEDICAL CANNABIS,IN-VIVO,EPILEPSY,NASAL,DELIVERY,BIOAVAILABILITY,FORMULATIONS,TOXICITY,DIAZEPAM}},
  language     = {{eng}},
  pages        = {{8}},
  title        = {{Pharmacokinetics of cannabidiol following intranasal, intrarectal, and oral administration in healthy dogs}},
  url          = {{http://doi.org/10.3389/fvets.2022.899940}},
  volume       = {{9}},
  year         = {{2022}},
}

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