Pharmacokinetics and physiologic effects of alprazolam after a single oral dose in healthy mares.

The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0-∞ ) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1-12 h). Alpha-hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted.

Renal replacement therapy in healthy adult horses.

BACKGROUND: Renal replacement therapy (RRT) has been implemented extensively in people to facilitate recovery from acute renal failure (ARF). RRT has not been explored in horses, but might provide a further treatment option in horses with ARF. OBJECTIVE: To investigate efficacy and safety of RRT in horses. ANIMALS: Five healthy adult horses. METHODS: A prospective study was performed on horses restrained in stocks and intravenously connected to a commercial RRT machine to allow continuous venovenous hemodiafiltration to be performed for 6 hours. The RRT machine was set at the following flow rates: blood flow rate 250 mL/min; dialysate rate 3,000 mL/h; prefilter replacement pump 3,000 mL/h; and postfilter replacement pump rate 2,000 mL/h. Balanced electrolyte solution was used as dialysate and replacement fluid. Heart rate, respiratory rate, body temperature, direct arterial blood pressure, urine output, and various clinicopathologic parameters were measured over the study period. RESULTS: Renal replacement therapy was successfully performed in horses, resulting in a mean creatinine clearance of 0.127 mL/kg/min (68.9 mL/min) and urea reduction ratio of 24%. No adverse effects were detected although a significant decrease in rectal temperature was observed (P ≤ .007). A significant increase in serum phosphorus (P ≤ .001) and decrease in BUN (P < .001) were also noted. A significant prolongation of prothrombin (P < .01) and partial thromboplastin time (P < .0001) were observed along with a decrease in platelet count (P ≤ .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Renal replacement therapy can safely and effectively be used in adult horses.

Clinical and immunomodulating effects of ketamine in horses with experimental endotoxemia.

BACKGROUND: Ketamine has immunomodulating effects both in vitro and in vivo during experimental endotoxemia in humans, rodents, and dogs. HYPOTHESIS: Subanesthetic doses of ketamine will attenuate the clinical and immunologic responses to experimental endotoxemia in horses. ANIMALS: Nineteen healthy mares of various breeds. METHODS: Experimental study. Horses were randomized into 2 groups: ketamine-treated horses (KET; n = 9) and saline-treated horses (SAL; n = 10). Both groups received 30 ng/kg of lipopolysaccharide (LPS, Escherichia coli, O55:B5) 1 hour after the start of a continuous rate infusion (CRI) of racemic ketamine (KET) or physiologic saline (SAL). Clinical and hematological responses were documented and plasma concentrations of tumor necrosis factor-α (TNF-α) and thromboxane B(2) (TXB(2)) were quantified. RESULTS: All horses safely completed the study. The KET group exhibited transient excitation during the ketamine loading infusion (P < .05) and 1 hour after discontinuation of administration (P < .05). Neutrophilic leukocytosis was greater in the KET group 8 and 24 hours after administration of LPS (P < .05). Minor perturbations of plasma biochemistry results were considered clinically insignificant. Plasma TNF-α and TXB(2) production peaked 1.5 and 1 hours, respectively, after administration of LPS in both groups, but a significant difference between treatment groups was not demonstrated. CONCLUSIONS AND CLINICAL IMPORTANCE: A subanesthetic ketamine CRI is well tolerated by horses. A significant effect on the clinical or immunologic response to LPS administration, as assessed by clinical observation, hematological parameters, and TNF-α and TXB(2) production, was not identified in healthy horses with the subanesthetic dose of racemic ketamine utilized in this study.

Plasma vasopressin concentrations in healthy foals from birth to 3 months of age.

BACKGROUND: Arginine vasopressin (AVP) has received increased attention in equine critical care but there is minimal information of AVP concentration in foals. The clinical usefulness of measuring AVP in ill foals depends on knowledge of age-related changes in AVP concentrations in healthy foals. HYPOTHESIS: Plasma AVP concentrations will be significantly different when measured from birth to 3 months of age in healthy foals. ANIMALS: Thirteen healthy university-owned foals. METHODS: Prospective, observational study. Blood was collected from healthy foals at birth and 3, 5, 7, 10, 14, 21, 28, 42, 56, and 84 days of age. Plasma was harvested and plasma AVP concentrations were determined by radioimmunoassay. RESULTS: No statistically significant differences were detected in plasma AVP concentrations over the study period. Plasma AVP concentrations over the entire study period was 6.2+/-2.5 pg/mL. CONCLUSIONS AND CLINICAL IMPORTANCE: There was no age-related variation in plasma AVP concentrations detected in healthy foals from birth to 3 months of age suggesting that AVP concentrations are similar across foals of these ages.