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  • Author or Editor: Khursheed R. Mama x
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Abstract

Objective—To determine the oral bioavailability, single and multidose pharmacokinetics, and safety of silibinin, a milk thistle derivative, in healthy horses.

Animals—9 healthy horses.

Procedures—Horses were initially administered silibinin IV and silibinin phospholipid orally in feed and via nasogastric tube. Five horses then consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week).

Results—Bioavailability of orally administered silibinin phospholipid was 0.6% PO in feed and 2.9% via nasogastric tube. During the multidose phase, silibinin had nonlinear pharmacokinetics. Despite this, silibinin did not accumulate when given twice daily for 7 days at the evaluated doses. Dose-limiting toxicosis was not observed.

Conclusions and Clinical Relevance—Silibinin phospholipid was safe, although poorly bio-available, in horses. Further study is indicated in horses with hepatic disease.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate antioxidant capacity and inflammatory cytokine gene expression in horses fed silibinin complexed with phospholipid.

Animals—5 healthy horses.

Procedures—Horses consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week). Dose-related changes in plasma antioxidant capacity, peripheral blood cell glutathione concentration and antioxidant enzyme activities, and blood cytokine gene expression were evaluated.

Results—Plasma antioxidant capacity increased throughout the study period with increasing dose. Red blood cell nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase I activity decreased significantly with increasing doses of silibinin phospholipid. No significant differences were identified in glutathione peroxidase activity, reduced glutathione or oxidized glutathione concentrations, or expression of tumor necrosis factor α, interleukin-1, or interleukin-2.

Conclusions and Clinical Relevance—Minor alterations in antioxidant capacity of healthy horses that consumed silibinin phospholipid occurred and suggest that further study in horses with liver disease is indicated.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate effects of injection with a nonsteroidal anti-inflammatory drug (NSAID) followed by oral administration of an NSAID on the gastrointestinal tract (GIT) of healthy dogs.

Animals—6 healthy Walker Hounds.

Procedures—In a randomized, crossover design, dogs were administered 4 treatments consisting of an SC injection of an NSAID or control solution (day 0), followed by oral administration of an NSAID or inert substance for 4 days (days 1 through 4). Treatment regimens included carprofen (4 mg/kg) followed by inert substance; saline (0.9% NaCl) solution followed by deracoxib (4 mg/kg); carprofen (4 mg/kg) followed by carprofen (4 mg/kg); and carprofen (4 mg/kg) followed by deracoxib (4 mg/kg). Hematologic, serum biochemical, and fecal evaluations were conducted weekly, and clinical scores were obtained daily. Endoscopy of the GIT was performed before and on days 1, 2, and 5 for each treatment. Lesions were scored by use of a 6-point scale.

Results—No significant differences existed for clinical data, clinicopathologic data, or lesion scores in the esophagus, cardia, or duodenum. For the gastric fundus, antrum, and lesser curvature, an effect of time was observed for all treatments, with lesions worsening from before to day 2 of treatments but improving by day 5.

Conclusions and Clinical Relevance—Sequential administration of NSAIDs in this experiment did not result in clinically important gastroduodenal ulcers. A larger study to investigate the effect of sequential administration of NSAIDs for longer durations and in dogs with signs of acute and chronic pain is essential to substantiate these findings.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the disposition of lidocaine after IV infusion in anesthetized horses undergoing exploratory laparotomy because of gastrointestinal tract disease.

Animals—11 horses (mean ± SD, 10.3 ± 7.4 years; 526 ± 40 kg).

Procedure—Lidocaine hydrochloride (loading infusion, 1.3 mg/kg during a 15-minute period [87.5 μg/kg/min]; maintenance infusion, 50 μg/kg/min for 60 to 90 minutes) was administered IV to dorsally recumbent anesthetized horses. Blood samples were collected before and at fixed time points during and after lidocaine infusion for analysis of serum drug concentrations by use of liquid chromatography-mass spectrometry. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis. Selected cardiopulmonary variables, including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2, were recorded. Recovery quality was assessed and recorded.

Results—Serum lidocaine concentrations paralleled administration, increasing rapidly with the initiation of the loading infusion and decreasing rapidly following discontinuation of the maintenance infusion. Mean ± SD volume of distribution at steady state, total body clearance, and terminal half-life were 0.70 ± 0.39 L/kg, 25 ± 3 mL/kg/min, and 65 ± 33 minutes, respectively. Cardiopulmonary variables were within reference ranges for horses anesthetized with inhalation anesthetics. Mean HR ranged from 36 ± 1 beats/min to 43 ± 9 beats/min, and mean MAP ranged from 74 ± 18 mm Hg to 89 ± 10 mm Hg. Recovery quality ranged from poor to excellent.

Conclusions and Clinical Relevance—Availability of pharmacokinetic data for horses with gastrointestinal tract disease will facilitate appropriate clinical dosing of lidocaine.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug.

ANIMALS 11 Thoroughbred horses enrolled in a fitness training program.

PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed.

RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration.

CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

Full access
in American Journal of Veterinary Research