Pharmacokinetics of chloramphenicol base after oral administration in adult horses.

OBJECTIVE To determine the pharmacokinetics of chloramphenicol base after PO administration at a dose of SO mg/kg (22.7 mg/lb) in adult horses from which food was not withheld. DESIGN Prospective crossover study. ANIMALS 5 adult mares. PROCEDURES Chloramphenicol base (SO mg/kg) was administered PO to each horse, and blood samples were collected prior to administration (0 minutes) and at 5, 10, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours thereafter. Following a washout period, chloramphenicol sodium succinate (25 mg/kg [11.4 mg/lb]) was administered IV to each horse, and blood samples were collected prior to administration (0 minutes) and at 3, 5, 10, 15, 30, and 45 minutes and 1, 2, 4, and 8 hours thereafter. RESULTS In horses, plasma half-life, volume of distribution at steady state, clearance, and area under the plasma concentration-time curve for chloramphenicol after IV administration ranged from 0.65 to 1.20 hours, 0.51 to 0.78 L/kg, 0.78 to 1.22 L/h/kg, and 20.5 to 32.1 h·µg/mL, respectively. The elimination half-life, time to maximum plasma concentration, maximum plasma concentration, and area under the plasma concentration-time curve after PO administration ranged from 1.7 to 7.4 hours, 0.25 to 2.00 hours, 1.52 to 5.45 µg/mL, and 10.3 to 21.6 h·µg/mL, respectively. Mean ± SD chloramphenicol bioavailability was 28 ± 10% and terminal half-life was 2.85 ± 1.32 hours following PO administration. CONCLUSIONS AND CLINICAL RELEVANCE Given that the maximum plasma chloramphenicol concentration in this study was lower than previously reported values, it is recommended to determine the drug's MIC for target bacteria before administration of chloramphenicol in adult horses.

Use of a constant rate infusion of insulin for the treatment of hyperglycemic, hypernatremic, hyperosmolar syndrome in an alpaca cria.

CASE DESCRIPTION: A 3-day-old 9.5-kg (21-lb) female alpaca cria was examined because of lethargy and anorexia. CLINICAL FINDINGS: Physical examination revealed hyperthermia, muscle fasciculations, and tremors of the head. Seizures were also observed, which indicated CNS dysfunction. Hyperosmolar syndrome (HOS) was diagnosed on the basis of hyperglycemia, hypernatremia, azotemia, high plasma osmolarity, and metabolic acidosis. TREATMENT AND OUTCOME: A constant rate infusion of regular insulin was administered with hypo-osmolar fluids to treat HOS, and blood glucose and sodium concentrations were successfully lowered. Neurologic deficits resolved with treatment, and the cria was discharged 11 days after admission. CLINICAL RELEVANCE: Administration of insulin as a bolus in addition to hypo-osmolar fluids has been advocated in the management of neonatal camelids with HOS. Administration of regular insulin via a constant rate IV infusion was used to successfully manage a neonatal camelid with HOS. This form of insulin administration may allow more control of glucose kinetics in these patients.

Successful treatment of a sinonasal cryptococcal granuloma in a horse.

CASE DESCRIPTION: A 12-year-old 500-kg (1,100-lb) American Quarter Horse mare was evaluated because of chronic mucopurulent, bloody discharge from the left nostril, inspiratory dyspnea, and respiratory noise. CLINICAL FINDINGS: The horse had severe inspiratory dyspnea and stertorous respiration with no airflow from the left nostril. A temporary tracheostomy was performed. Endoscopy revealed a tan mass protruding from the left middle nasal meatus into the left common nasal meatus; it extended caudally into the nasopharynx and around the caudal edge of the nasal septum into the right nasal cavity. Radiographically, a soft tissue opacity was evident in most of the left nasal cavity and left paranasal sinuses. Cytologic examination of mass tissue revealed evidence of pyogranulomatous rhinitis; thickly encapsulated, budding yeast typical of Cryptococcus neoformans were detected. TREATMENT AND OUTCOME: While the horse was sedated and in a standing position, the fungal granuloma was removed from the paranasal sinuses. Treatment with fluconazole (5 mg/kg [2.27 mg/lb], PO, q 24 h for 4 weeks) was initiated; enilconazole (50 mL of a 10% solution) was instilled into the paranasal sinuses every other day (7 lavages). Six weeks after surgery, infection had not recurred and epithelialization appeared normal in the left paranasal sinuses. CLINICAL RELEVANCE: In horses with cryptococcosis of the paranasal sinuses, surgical removal of granulomatous lesions and systemic and topical administrations of antifungal drugs may be curative. Successful surgery may be performed in standing horses. Concommitant removal of a large portion of the conchae allows follow-up rhinoscopic evaluation of the paranasal sinuses.

Effects of intravenously administrated omeprazole on gastric juice pH and gastric ulcer scores in adult horses.

The study was performed to evaluate the efficacy of omeprazole powder in sterile water, administered intravenously, on gastric juice pH in adult horses with naturally occurring gastric ulcers. Omeprazole (0.5 mg/kg, IV) was administered once daily for 5 days to 6 adult horses with gastric ulcers. Gastric juice was aspirated through the biopsy channel of an endoscope and pH was measured before and 1 hour after administration of omeprazole on day 1, and then before and after administration of omeprazole on day 5. Gastric ulcer scores were recorded on day 1 before administration of omeprazole and on day 5, 23 hours after the 4th daily dose. Gastric juice pH and ulcer scores were compared between the times. When compared with the pre-injection value (2.01 +/- 0.42), mean +/- SD gastric juice pH was significantly higher when measured 1 hour after administration of the initial dose (4.35 +/- 2.31), and before (5.27 +/- 1.74) and 1 hour after (7.00 +/- 0.25) administration of omeprazole on day 5. Nonglandular gastric ulcer number score significantly decreased from a mean +/- SD of 3.2 +/- 0.80 to 2.0 +/- 1.1, but nonglandular gastric ulcer severity score remained the same. Few glandular ulcers were seen in the study, and scores did not change. Because of its potent and long duration of action on gastric juice pH, this intravenous formulation of omeprazole may show promise for treatment of equine gastric ulcer syndrome (EGUS) in horses with dysphagia, gastric reflux, or other conditions that restrict oral intake of omeprazole paste. Aspiration of gastric juice and measurement of pH can be of use to determine whether the desired pH > 4.0 has been reached after omeprazole treatment.

Evaluation of the combined dexamethasone suppression/ thyrotropin-releasing hormone stimulation test for detection of pars intermedia pituitary adenomas in horses.

BACKGROUND: A combined dexamethasone (DEX) suppression/thyrotropin-releasing hormone (TRH) test (DEX/TRH test) has been developed to evaluate horses for presence of a pars intermedia pituitary adenoma (PIPA), but to the authors' knowledge, the accuracy of this test has not been previously determined. HYPOTHESIS: The sensitivity and specificity of the DEX/TRH test can be determined by comparing test results with histopathologic examination findings. ANIMALS: Age of 42 horses of various breeds ranged from 2 to 33 years. METHODS: Plasma cortisol concentration was measured before and 24 hours after IV administration of 40 microg of DEX/kg of body weight, and before and 30 minutes after IV administration of 1 mg of TRH that had been given 3 hours after the injection of DEX. Results of the DEX/TRH test were considered positive if either the plasma cortisol concentration exceeded 10 ng/mL 24 hours after DEX administration, or if the change in plasma cortisol concentration 30 minutes after injection of TRH was > or = 66% above the 3-hour baseline. Diagnosis of PIPA was determined by histologic examination of the pituitary gland. RESULTS: PIPA was detected in 17 of 42 (40%) horses. The DEX/TRH test had sensitivity, specificity, positive predictive value, and negative (NPV) predictive value of 88, 76, 71, and 90%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The combined DEX/TRH test was more sensitive than either of its component tests and had a high NPV, but was not as specific as the TRH component alone (92%). The DEX/TRH test should be used to screen older horses for PIPA.

Effect of a 24-hour infusion of an isotonic electrolyte replacement fluid on the renal clearance of electrolytes in healthy neonatal foals.

OBJECTIVE: To determine the effects of a 24-hour infusion of an isotonic electrolyte replacement fluid (IERF) on weight, serum and urine electrolyte concentrations, and other clinicopathologic variables in healthy neonatal foals. ANIMALS: 4 healthy 4-day-old foals. DESIGN: Prospective study. PROCEDURE: An IERF was administered to each foal at an estimated rate of 80 mL/kg/d (36.4 mL/lb/d) for 24 hours. Body weight was measured before and after the infusion period. Urine was collected via catheter during 4-hour periods; blood samples were collected at 4-hour intervals. Variables including urine production; urine and serum osmolalities; sodium, potassium, and chloride concentrations in urine and serum; urine and serum creatinine concentrations; urine osmolality-to-serum osmolality ratio (OsmR); transtubular potassium gradient (TTKG); and percentage creatinine clearance (Cr(cl)) of electrolytes were recorded at 0, 4, 8, 12, 16, 20, and 24 hours during the infusion period. Immediately after the study period, net fluid and whole-body electrolyte changes from baseline values were calculated. RESULTS: Compared with baseline values, urine and serum sodium and chloride serum concentrations, urine and serum osmolalities, OsmR, and percentage Cr(cl) of sodium and chloride were significantly increased at various time points during the infusion; urine production did not change significantly. After 24 hours, weight, TTKG, serum creatinine concentration, and whole-body potassium had significantly decreased from baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of an IERF containing a physiologic concentration of sodium may not be appropriate for use in neonatal foals that require maintenance fluid therapy.

Effects of oral administration of levothyroxine sodium on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone in healthy adult mares.

OBJECTIVE: To determine the effects of levothyroxine sodium (L-T4) on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone (TRH) in euthyroid horses. ANIMALS: 12 healthy adult mares. PROCEDURE: 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provided for 2 weeks. Four additional horses remained untreated. Serum concentrations of total triiodothyronine (tT3), total thyroxine (tT4), free T3 (fT3), free T4 (fT4), and thyroid-stimulating hormone (TSH) were measured in samples obtained at weeks 0, 2, 4, 6, and 8; 1.2 mg of TRH was then administered i.v., and serum concentrations of thyroid gland hormones were measured 2 and 4 hours after injection. Serum reverseT3 (rT3) concentration was also measured in the samples collected at weeks 0 and 8. RESULTS: Treated horses lost a significant amount of weight (median, 19 kg). Significant treatment-by-time effects were detected for serum tT3, tT4, fT3, fT4, and TSH concentrations, and serum tT4 concentrations were positively correlated (r, 0.95) with time (and therefore dosage) in treated horses. Mean +/- SD serum rT3 concentration significantly increased in treated horses (3.06 +/- 0.51 nmol/L for week 8 vs 0.74 +/- 0.22 nmol/L for week 0). Serum tT3, tT4, fT3, and TSH concentrations in response to TRH injections differed significantly between treated and untreated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of levothyroxine sodium increased serum tT4 concentrations and blunted responses toTRH injection in healthy euthyroid horses.

Effects of oral administration of levothyroxine sodium on concentrations of plasma lipids, concentration and composition of very-low-density lipoproteins, and glucose dynamics in healthy adult mares.

OBJECTIVE: To evaluate glucose and lipid metabolism in healthy adult horses administered levothyroxine sodium (L-T4). ANIMALS: 12 healthy adult mares. PROCEDURE: 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provide between 7 AM and 8 AM in the morning grain meal for 2 weeks. Four additional horses remained untreated. Serum concentrations of nonesterified fatty acids, triglyceride (TG), total cholesterol (TC), and very-low-density lipoprotein (VLDL) were measured and composition of VLDL examined in samples obtained between 8 AM and 9 AM at weeks 0, 2, 4, 6, and 8. Glucose dynamics were assessed by use of a combined IV glucose-insulin tolerance test (IVGITT) conducted before and at the end of the 8-week treatment period. Data for each combined IVGITT were interpreted by use of the minimal model. RESULTS: Plasma TG, TC, and VLDL concentrations significantly decreased over time in treated horses. At the completion of the 8-week treatment period, mean plasma VLDL concentration was 46% of the mean value for week 0 in treated horses. Insulin sensitivity significantly increased (> 2-fold) in treated horses, but glucose effectiveness and net insulin response were not affected. Levothyroxine sodium significantly increased the rate of insulin disposal. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L-T4 decreases blood lipid concentrations, improves insulin sensitivity, and increases insulin disposal in horses. Levothyroxine sodium may have potential as a treatment for horses with reduced insulin sensitivity.

Mice heterozygous for Atp10c, a putative amphipath, represent a novel model of obesity and type 2 diabetes.

Atp10c is a novel type IV P-type ATPase and is a putative phospholipid transporter. The purpose of this study was to assess the overall effect of the heterozygous deletion of Atp10c on obesity-related phenotypes and metabolic abnormalities in mice fed a high-fat diet. Heterozygous mice with maternal inheritance of Atp10c were compared with heterozygous mice with paternal inheritance of Atp10c and wild-type controls. Body weight, adiposity index, and plasma insulin, leptin and triglyceride concentrations were significantly greater in the mutants inheriting the deletion maternally compared with their sex- and age-matched control male mice fed a 10% fat (% energy) diet and female mice fed a 45% fat (% energy) diet. Glucose and insulin tolerance tests were performed after mice consumed the diets for 4 and 8 wk. Mutants had altered glucose tolerance and insulin response compared with controls, suggesting insulin resistance in both sexes. Mice were killed at 12 wk and routine gross and histological evaluations of the liver, pancreas, adipose tissue, and heart were performed. Histological evaluation showed micro- and macrovesicular lipid deposition within the hepatocytes that was more severe in the mutant mice than in age-matched controls. Although sex differences were observed, our data suggest that heterozygous deletion along with an unusual pattern of maternal inheritance of the chromosomal region containing the single gene, Atp10c, causes obesity, type 2 diabetes, and nonalcoholic fatty liver disease in these mice.