RT Journal Article
T1 Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders
A1 Fernández Trapero, María
A1 Pérez Díaz, Carmen
A1 Espejo Porras, Francisco
A1 Lago Femia, Eva de
A1 Fernández Ruiz, Javier
AB The phytocannabinoid-based medicine Sativex® is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), ∆9-tetrahydrocannabinol (∆9-THC) and its metabolite 11-hydroxy-∆9-THC. Maximal plasma concentrations of both ∆9-THC (Cmax = 18.5 ng/mL) and CBD (Cmax = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (∆9-THC: Cmax = 24.5 ng/mL; CBD: Cmax = 15.2 ng/mL). 11-hydroxy-∆9-THC, which is mainly formed in the liver from ∆9-THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and ∆9-THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1–2 h and suggested progressive accumulation after the multiple dose treatment.
PB MDPI
SN 2218-273X
YR 2020
FD 2020-02-11
LK https://hdl.handle.net/20.500.14352/7928
UL https://hdl.handle.net/20.500.14352/7928
LA eng
NO Ministerio de Economía y Competitividad (MINECO)
NO Comunidad de Madrid
DS Docta Complutense
RD 13 sept 2024