Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations.

BACKGROUND: Intravenous pharmacokinetics and oral bioavailability of cannabidiol (CBD) with different formulations have not been investigated in horses and may represent a starting point for clinical studies. OBJECTIVES: To describe pharmacokinetics after intravenous and oral administrations with oil and micellar formulations and simulate different treatments. STUDY DESIGN: Single intravenous experiment and two-way randomised oral experiments, Latin-square design. METHODS: Eight healthy horses received intravenous CBD at 1.00 mg/kg dose, oral CBD in sesame oil and in micellar formulation, both at 10.00 mg/kg. Concentrations were measured using LC-MS/MS and fitted by nonlinear mixed effect modelling. Parameters obtained were used to simulate single and multiple treatments at steady state. RESULTS: Intravenous and oral concentrations were simultaneously fitted using a three-compartment model. Final estimates indicate that CBD has a volume of distribution of 36 L/kg associated with a systemic clearance of 1.46 L/h/kg and half-lives ranged between 24 and 34 h. Oral bioavailability was close to 14% for both oral administrations. Simulated dose regimen of CBD every 12 and 24 h predicted similar percentages to reach effective plasma concentration with both oral formulation at 10.00 mg/kg. MAIN LIMITATIONS: A small horse population was used (8 horses per trial). CONCLUSIONS AND CLINICAL IMPORTANCE: Oral bioavailability was low at the doses studied but fell within the range described for horse and other species. CBD had a high steady-state volume of distribution, a high clearance and long half-lives. No adverse reactions were detected at any dose or route. The micellar formulation showed a faster absorption and higher concentration peak, while the oil formulation presented lower levels, but more maintained over time. Simulations predicted that both could be useful in multiple oral dose treatments. These results indicated that CBD could be of interest, but further studies are needed to evaluate its clinical use in horses.

Accelerometric Changes before and after Capacitive Resistive Electric Transfer Therapy in Horses with Thoracolumbar Pain Compared to a SHAM Procedure.

Capacitive resistive electric transfer (CRET), a radiofrequency at 448 kHz, increases flexibility in quadricep muscles of human athletes. To assess whether CRET would result in clinical and biomechanical improvements in horses with thoracolumbar pain, 18 sport horses were divided into two groups: CRET (n = 9), subjected to four CRET sessions, during two consecutive weeks, and SHAM (n = 9), subjected to the same procedure with the device off. Clinical examination and accelerometry were performed before and after the four sessions. During the study, horses were in training and in active competition, and did not receive any other treatment. Mann-Whitney and a Wilcoxon matched pair tests were used to compare between the SHAM and CRET groups and before and after the intervention, respectively. CRET horses showed increased dorsoventral (p < 0.002), mediolateral and total power (p < 0.01) after the intervention, suggesting increased back flexibility. SHAM horses did not show any of these modifications after the intervention. No changes were found in the dorsoventral displacement of the gravity center in either group. Thoracolumbar pain decreased one degree after CRET (p = 0.002), and it did not change after SHAM. Epaxial muscle pain decreased two degrees after CRET (p = 0.03) and one degree after SHAM (p = 0.01). These results reflected that CRET therapy would increase back flexibility and decrease thoracolumbar and epaxial pain.

Combined Effects of Water Depth and Velocity on the Accelerometric Parameters Measured in Horses Exercised on a Water Treadmill.

Horse trainers often claim that exercise on a water treadmill (WT) leads to a greater muscle power and development compared to terrestrial locomotion, because of the greater viscosity of water compared to air. This research assesses locomotor changes measured with accelerometers fixed in the pectoral region and in the sacrum midline in six horses subjected to exercise sessions of 40 min duration on a WT without water (DT), and with water at the depth of fetlock (FET) and carpus (CAR) with velocities of 6 km/h and at the depth of stifle (STF) at 5 km/h. Another five horses performed the same exercise sessions but always with a velocity of 5 km/h. Total power increased from DT to FET and CAR, without significant differences between CAR and STF depths when the velocity was the same. However, a significant decrease was found when the velocity was reduced. The greater total power with water was distributed mainly to the dorsoventral axis, with significant increases in dorsoventral displacement and dorsoventral power. Both parameters were significantly affected by velocity and water depth. In conclusion, total and dorsoventral powers increased with velocity and water depth, leading to reduction in longitudinal and mediolateral power, during exercise on a WT.

Capacitive resistive electric transfer modifies gait pattern in horses exercised on a treadmill.

BACKGROUND: Capacitive resistive electric transfer (CRET), a radiofrequency at 448 kHz, resulted in increased superficial and deep temperature and hemoglobin saturation, faster elimination of metabolic and inflammatory products and enhanced sport performance in humans. This research aims to investigate whether the application of CRET affects the locomotor pattern in horses and to assess whether an accumulative effect appears when two CRET sessions are applied two consecutive days. METHODS: Nine horses were subjected to two CRET sessions applied in both right and left sides of neck, shoulder, back and croup. The horses were exercised on a treadmill, at walk and at trot, before CRET application and at 2, 6 and 12 h after. A second CRET session was applied next day, and the animals were evaluated again at the same times (i.e. at 26, 30 and 36 h after the first session). Between 5 and 7 days later, the same horses were subjected to a sham procedure and they were evaluated in the same times as in the CRET experiment. During treadmill exercise, locomotor parameters were measured with a triaxial accelerometer fixed in the pectoral region and in the sacrum midline. RESULTS: The sham procedure did not affect any of the accelerometric variables studied. CRET applications resulted in greater total powers, which resulted in absolute increased dorsoventral, mediolateral and longitudinal powers. However, a reduction in dorsoventral power expressed as a percentage of total power was found. Stride regularity increased. The greater total power resulted in longer stride length and because the velocity was kept fixed on the treadmill, stride frequency decreased. An accumulative effect of CRET application was only found in stride length and frequency. CONCLUSIONS: It appears that CRET is a useful technique to enhance power and to elongate the stride at defined walk and trot velocities. The effect of these changes on performance should be studied for horses competing in different sport disciplines.