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Abstract

Objective—To assess pharmacokinetics of pregabalin in horses after a single intragastric or IV dose.

Animals—5 healthy adult mares.

Procedures—Horses received 1 dose of pregabalin (approx 4 mg/kg) via nasogastric tube in a crossover-design study; after a 3-week washout period, the same dose was administered IV. Food was not withheld. Plasma pregabalin concentrations in samples obtained 0 to 36 hours after administration were measured by use of ultra-performance liquid chromatography with triple quadrupole tandem mass spectrometry. Pharmacokinetic variables were estimated by means of noncompartmental analysis.

Results—Mild sedation was observed in 2 horses following intragastric and IV pregabalin administration. Signs of mild, transient colic or behavioral abnormalities were observed in all horses following IV administration. After intragastric administration, median (range) maximal plasma concentration was 5.0 μg/mL (4.4 to 6.7 μg/mL), time to maximal plasma concentration was 1. 0 hour (0.5 to 2.0 hours), elimination half-life was 8.0 hours (6.2 to 9.4 hours), and area under the curve from time 0 to infinity (AUC0–∞) was 47.2 μg·h/mL (36.4 to 58.4 μg·h/mL). After IV administration, initial concentration was 22.2 μg/mL (19.8 to 27.7 μg/mL), elimination half-life was 7.74 hours (6.94 to 8.17 hours), and AUC0–∞ was 48.3 μg·h/mL (44.8 to 57.2 μg·h/mL). Bioavailability was 97.7% (80.7% to 109.8%). Median predicted values for minimal, mean, and maximal steady-state plasma concentrations after intragastric administration assuming an 8-hour dosing interval were 3.9, 5.3, and 6.3 μg/mL, respectively.

Conclusions and Clinical Relevance—At a simulated intragastric dosage of approximately 4 mg/kg every 8 hours, median pregabalin steady-state plasma concentration in healthy horses was within the therapeutic range reported for humans. Therapeutic concentrations and safety of this dosage have not been established in horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics and hemodynamic effects of trazodone after IV and oral administration in dogs and bioavailability after oral administration.

Animals—6 adult Beagles.

Procedures—Dogs received trazodone HCl (8 mg/kg) orally and IV in a randomized controlled crossover design. Blood samples were collected at various times after administration. Heart rates and indirectly measured blood pressures of dogs and plasma concentrations and pharmacokinetics of trazodone were determined.

Results—Following IV administration, the mean ± SD elimination half-life, apparent volume of distribution, and plasma total body clearance were 169 ± 53 minutes, 2.53 ± 0.47 L/kg, and 11.15 ± 3.56 mL/min/kg, respectively. Following oral administration, the mean ± SD elimination half-life and absolute bioavailability were 166 ± 47 minutes and 84.6 ± 13.2%, respectively. Maximum plasma concentration following oral administration was 1.3 ± 0.5 μ/mL, and time to maximum plasma concentration was 445 ± 271 minutes. After IV administration, all dogs immediately developed transient tachycardia (184.3 ± 8.0 beats/min), and 3 of 6 dogs developed aggression. Increase in heart rate was significantly associated with increase in plasma drug concentration following IV administration.

Conclusions and Clinical Relevance—Results of this study indicated oral administration of trazodone resulted in acceptable absolute bioavailability, with substantial variability in time to maximum plasma concentration. Individualized approaches in dosing intervals may be necessary for dogs receiving oral trazodone. An orally administered dose of 8 mg/kg was well tolerated in dogs; IV administration of a dose of 8 mg/kg caused substantial adverse effects, including tachycardia and behavior disinhibition.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the frequency of spontaneous canine herpesvirus-1 (CHV-1) reactivation and ocular viral shedding in latently infected dogs and the effect of topical ocular administration of cyclosporine.

Animals—8 mature Beagles with experimentally induced latent CHV-1 infection.

Procedures—Following induction of primary ocular CHV-1 infection, the presence of reactivatable CHV-1 latency was confirmed by systemically administering prednisolone to the dogs. Dogs were then monitored for 36 weeks via clinical examination and conjunctival sample CHV-1 PCR assay performed at 4-day intervals and CHV-1 virus neutralization antibody assay performed at 2-week intervals. During weeks 16 to 32, dogs were administered 0.2% cyclosporine ointment in both eyes twice daily and blood cyclosporine concentrations were monitored. During weeks 33 to 36, the presence of reactivatable CHV-1 latency was reconfirmed via systemic administration of prednisolone.

Results—Reactivation of latent CHV-1 was not detected via clinical examination or viral shedding during the initial 32 weeks, including before and during topical ocular administration of cyclosporine, and there were no significant differences in CHV-1 virus neutralization titer increases between the study periods. Blood cyclosporine concentrations were less than assay detection limits in all dogs on the sampling days. Systemic administration of corticosteroids repeatedly resulted in ocular disease and viral shedding.

Conclusions and Clinical Relevance—Spontaneous CHV-1 reactivation did not occur frequently in latently infected mature dogs, and this was not altered by topical ocular administration of cyclosporine. This characteristic may be a factor contributing to the lower frequency of recurrent herpetic ocular disease in dogs relative to other host species and their associated alphaherpesviruses.

Full access
in American Journal of Veterinary Research