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Abstract

OBJECTIVE To determine whether target values for pharmacokinetic-pharmacodynamic (PK-PD) indices against selected canine pathogens were achievable for pradofloxacin in various canine fluids and leukocytes.

ANIMALS 8 healthy adult hounds (experiments 1 and 2) and 6 healthy adult dogs (experiment 3).

PROCEDURES In 3 experiments, pradofloxacin (3, 6, or 12 mg/kg) and enrofloxacin (5 or 10 mg/kg) were orally administered once a day for 5 days, and blood, interstitial fluid (ISF), and other fluid samples were collected at various points. Sample drug concentrations were measured, and noncompartmental pharmacokinetic analysis was performed; then, PK-PD indices (ratios between maximum observed concentration [Cmax] and minimum inhibitory or mutant prevention concentrations) were determined for 7 bacterial species.

RESULTS PK-PD values for pradofloxacin at 3 mg/kg were approximately 5 times as high in leukocyte versus plasma and were lowest in CSF, synovial fluid, and aqueous humor. No significant differences were noted between serum and ISF. Value ratios for serum versus other body fluids were numerically higher for pradofloxacin (vs enrofloxacin) for all fluid types except CSF and aqueous humor. Target PK-PD values were exceeded for pradofloxacin against all 7 bacterial species in leukocytes and against all species except Bacteroides spp in serum and ISF. Enrofloxacin achieved the target Cmax-to-minimum inhibitory concentration ratio against Pasteurella multocida in serum, ISF, and leukocytes and for Staphylococcus pseudintermedius in serum and leukocytes. A Cmax-to-mutant prevention concentration ratio ≥ 1 against Eschericha coli was achieved for pradofloxacin at 6 mg/kg.

CONCLUSIONS AND CLINICAL RELEVANCE These findings supported once-daily oral administration of pradofloxacin to dogs at the currently recommended dose (7.5 mg/kg).

Full access
in American Journal of Veterinary Research

Summary

Twenty-five animals (21 dogs and 4 cats) in which hepatobiliary scintigraphy (hbs) was performed between 1982 and 1989 were included in a retrospective study to determine the utility of hbs for diagnosis of extrahepatic biliary obstruction. Final diagnoses, which were based on liver biopsy results and surgical findings in all animals, were hepatocellular disease alone (n = 17), hepatocellular disease and extrahepatic biliary obstruction (n = 7), and normal liver (n = 1). Hepatobiliary scintigraphy was performed by use of 99mTc-diisopropyl iminodiacetic acid in all cases. All 7 cases of extrahepatic biliary obstruction were confirmed at surgery. In animals with biliary obstruction, hbs failed to demonstrate radiolabel within either the gallbladder or intestine at any time. Using nonvisualization of the intestine by 180 minutes as the scintigraphic criterion for diagnosis of biliary obstruction, sensitivity was 83% and specificity was 94% in this series. Hepatobiliary scintigraphy was concluded to be an accurate indicator of extrahepatic biliary obstruction in this group of animals. High serum bilirubin concentration at the time hbs was performed did not appear to reduce the diagnostic usefulness of the scintigraphic findings.

Free access
in Journal of the American Veterinary Medical Association

Abstract

Objective

To determine existence of portal and systemic bacteremia in dogs with induced severe hepatic disease, compared with clinically normal dogs, before and after vena caval banding.

Animals

6 control dogs and 10 dogs with induced severe hepatic disease and multiple portosystemic shunts (PSS).

Procedure

Dogs of the diseased group were given dimethylnitrosamine (2 mg/kg of body weight, PO) twice weekly until multiple PSS developed. Surgery was performed on dogs of both groups, and blood for baseline aerobic and anaerobic bacterial culture was collected from catheters placed in the portal and hepatic veins and caudal vena cava. All dogs underwent vena caval banding, and blood for aerobic and anaerobic bacterial culture was collected from the portal and hepatic venous catheters at 120, 240, and 360 minutes after banding.

Results

Compared with control dogs (16% gram-positive and 84% gram-negative bacteria), diseased dogs had significantly higher percentage of gram-positive bacteria (42% of positive culture results, P ≤ 0.01) and significantly lower percentage of gram-negative bacteria (58% of positive culture results, P ≤ 0.01) isolated. Pseudomonas aeruginosa was isolated most frequently from dogs of both groups; more than 1 organism was isolated from 5 dogs of each group. Antimicrobial susceptibility included that to aminoglycosides (particularly amikacin), fluorinated quinolones, and imipenem.

Conclusions

Portal and systemic, predominantly gram-negative, bacteremia is present in catheterized, clinically normal dogs and dogs with dimethylnitrosamine-induced hepatic disease and multiple PSS. (Am J Vet Res 1999;60:181-185)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To document presence of endotoxin in portal and systemic blood in a model of canine multiple portosystemic shunts (PSS), and compare values in clinically normal dogs, before and after vena caval banding.

Animals

6 control dogs and 10 dogs with dimethylnitrosamine-induced multiple PSS that were subjected to vena caval banding.

Procedure

Dimethylnitrosamine was administered orally (2 mg/kg of body weight, twice weekly) to the 10 dogs in the diseased group until multiple PSS developed. Surgery was then performed on all 16 dogs (both groups), and shunts were confirmed in the diseased dogs. Blood was collected from the portal vein, hepatic vein, and caudal vena cava for baseline endotoxin determination and aerobic and anaerobic blood culturing. Baseline pressure measurements were taken from the portal venous catheter; then vena caval banding was performed. Blood for endotoxin determinations was taken from all vessels 20, 40, 60, 120, 240, and 360 minutes after banding; portal pressure measurements were taken at the same time as sample acquisition. Blood for culturing was taken from the portal and hepatic venous catheters at 120, 240, and 360 minutes after banding.

Results

Dogs in the diseased group had significantly greater overall presence of endotoxin in the portal vein (P ≤ 0.0002), hepatic vein (P ≤ 0.0001), and caudal vena cava (P ≤ 0.0004) than did control dogs. With respect to time, endotoxin presence was greater in the diseased group before banding (P ≤ 0.0002), and at 20 (P ≤ 0.0008), 40 (P ≤ 0.002), 60 (P ≤ 0.006), and 120 (P ≤ 0.01) minutes after banding.

Conclusions

Endotoxemia is more frequently present in catheterized dogs with dimethylnitrosamine-induced hepatic disease and multiple PSS, compared with clinically normal dogs. Additionally, portal pressure changes induced by vena caval banding did not affect endotoxemia.

Clinical Relevance

Endotoxemia may exist in dogs with hepatic disease and multiple PSS, and should be kept in mind when formulating treatment (particularly antimicrobial selection) for dogs with suspected endotoxemia. (Am J Vet Res 1997;58:83–88)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effect of an indwelling nasogastric tube on gastric emptying of liquids in horses.

Animals—9 healthy adult horses.

Procedure—A randomized block crossover design was used. For treatment group horses, a nasogastric tube was placed and 18 hours later, acetaminophen was administered; the nasogastric tube remained in place until the experiment was complete. For control group horses, a nasogastric tube was passed into the stomach, acetaminophen was administered, and the nasogastric tube was removed immediately. Serial blood samples were collected 15 minutes before and after administration of acetaminophen. Serum concentration of acetaminophen was determined by use of fluorescence polarization immunoassay. The variables, time to maximum acetaminophen concentration (Tmax) and the appearance constant for acetaminophen (Kapp), were determined. The values for Kapp and Tmax in horses with and without prolonged nasogastric tube placement were compared.

Results—No significant difference was found in Kapp between horses with and without prolonged nasogastric tube placement; the median difference in Kapp was 0.01 min–1 (range, –0.48 to 0.80 min–1). No significant difference was found in Tmax between horses with and without prolonged nasogastric tube placement; the median difference in Tmax was 5 minutes (range, –30 to 50 minutes). Reanalysis of data following the removal of possible outlier values from 1 horse resulted in a significant difference in Tmax between horses with and without prolonged nasogastric tube placement.

Conclusions and Clinical Relevance—Although no clinically important impact of 18 hours of nasogastric intubation was found on gastric emptying in healthy horses, considerable variability in Kapp and Tmax was found among horses. (Am J Vet Res 2005;66:642–645)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether therapeutic concentrations of levetiracetam can be achieved in cats and to establish reasonable IV and oral dosing intervals that would not be associated with adverse effects in cats.

Animals—10 healthy purpose-bred cats.

Procedures—In a randomized crossover study, levetiracetam (20 mg/kg) was administered orally and IV to each cat. Blood samples were collected 0, 10, 20, and 40 minutes and 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours after administration. Plasma levetiracetam concentrations were determined via high-performance liquid chromatography.

Results—Mean ± SD peak concentration was 25.54 ± 7.97 μg/mL. The mean y-intercept for IV administration was 37.52 ± 6.79 μg/mL. Half-life (harmonic mean ± pseudo-SD) was 2.95 ± 0.95 hours and 2.86 ± 0.65 hours for oral and IV administration, respectively. Mean volume of distribution at steady state was 0.52 ± 0.09 L/kg, and mean clearance was 2.0 ± 0.60 mL/kg/min. Mean oral bioavailability was 102 ± 39%. Plasma drug concentrations were maintained in the therapeutic range reported for humans (5 to 45 μg/mL) for at least 9 hours after administration in 7 of 10 cats. Only mild, transient hypersalivation was evident in some cats after oral administration.

Conclusions and Clinical Relevance—Levetiracetam (20 mg/kg) administered orally or IV to cats every 8 hours should achieve and maintain concentrations within the therapeutic range for humans. Levetiracetam administration has favorable pharmacokinetics for clinical use, was apparently tolerated well, and may be a reasonable alternative antiepileptic drug in cats.

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare efficacy and safety of treatment with phenobarbital or bromide as the first-choice antiepileptic drug (AED) in dogs.

Design—Double-blinded, randomized, parallel, clinical trial.

Animals—46 AED-naïve dogs with naturally occurring epilepsy.

Procedures—Study inclusion was based on age, history, findings on physical and neurologic examinations, and clinicopathologic test results. For either phenobarbital treatment (21 dogs) or bromide treatment (25), a 7-day loading dose period was initiated along with a maintenance dose, which was adjusted on the basis of monthly monitoring. Efficacy and safety outcomes were compared between times (baseline and study end [generally 6 months]) and between drugs.

Results—Phenobarbital treatment resulted in eradication of seizures (17/20 [85%]) significantly more often than did bromide (12/23 [52%]); phenobarbital treatment also resulted in a greater percentage decrease in seizure duration (88 ± 34%), compared with bromide (49 ± 75%). Seizure activity worsened in 3 bromide-treated dogs only. In dogs with seizure eradication, mean ± SD serum phenobarbital concentration was 25 ± 6 μg/mL (phenobarbital dosage, 4.1 ± 1.1 mg/kg [1.9 ± 0.5 mg/lb], PO, q 12 h) and mean serum bromide concentration was 1.8 ± 0.6 mg/mL (bromide dosage, 31 ± 11 mg/kg [14 ± 5 mg/lb], PO, q 12 h). Ataxia, lethargy, and polydipsia were greater at 1 month for phenobarbital-treated dogs; vomiting was greater for bromide-treated dogs at 1 month and study end.

Conclusions and Clinical Relevance—Both phenobarbital and bromide were reasonable first-choice AEDs for dogs, but phenobarbital was more effective and better tolerated during the first 6 months of treatment.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To describe bacteria isolated from reproductive tracts of mares and to examine the extent and patterns of resistance to antimicrobials commonly used for treatment of endometritis.

Design—Retrospective case series.

Sample—8,296 uterine swab, lavage, or biopsy samples obtained between January 2003 and December 2008 from 7,665 horses in central Florida.

Procedures—Results of bacterial culture and antimicrobial susceptibility testing were obtained for uterine swab, lavage, and biopsy samples collected from mares undergoing a routine breeding examination or examined because of a reproductive disorder. Bacterial organisms were identified by means of standard techniques, and proportions of samples resistant to various antimicrobials were determined.

Results—At least 95% of samples (n = 1,451) were collected with uterine swabs. Potentially pathogenic organisms were cultured from 2,576 (31%) samples, with Escherichia coli (n = 729 [29%]) and β-hemolytic Streptococcus equi subsp zooepidemicus (733 [28%]) being most common. Resistance to antimicrobials changed over time for E coli, S equi subsp zooepidemicus, and Enterobacteriaceae isolates. Overall, E coli was most resistant to trimethoprim-sulfonamide and ampicillin and least to amikacin and enrofloxacin. For S equi subsp zooepidemicus, resistance was greatest to oxytetracycline and enrofloxacin and least to ceftiofur and ticarcillin with or without clavulanic acid. Inflammatory response was greater for S equi subsp zooepidemicus.

Conclusions and Clinical RelevanceE coli and S equi subsp zooepidemicus were the most common pathogens recovered from uterine samples, with S equi subsp zooepidemicus more commonly associated with inflammation. Antimicrobials most commonly used empirically to treat endometritis are appropriate on the basis of these data. However, as antimicrobial resistance changes over time, susceptibility assays should aid antimicrobial selection.

Full access
in Journal of the American Veterinary Medical Association

SUMMARY

Objective

To determine disposition of cyproheptadine hydrochloride in cats after intravenous or oral administration of a single dose.

Animals

6 healthy cats.

Procedure

A randomized crossover design was used, and each cat was studied after intravenous (2 mg) and oral (8 mg) administration of cyproheptadine. Blood samples were collected at fixed time intervals after drug administration, and serum cyproheptadine concentration was determined by means of polarized immunofluorescence.

Results

Mean (± SD) residence time was significantly longer after oral (823 ± 191 minutes) than after intravenous (339 ±217 minutes) administration, but no significant differences were detected between other pharmacokinetic parameters after oral and intravenous administration. Mean ± SD oral bioavailability was 1.01 ± 0.36. Mean elimination half-life after oral administration was 12.8 ± 9.9 hours. Peak extrapolated cyproheptadine concentration was 669 ± 206 ng/ml. Only 1 cat developed adverse effects (transient vocalization).

Conclusions

Cyproheptadine appeared to be well tolerated in cats and had high bioavailability after oral administration. The mean elimination half-life of 12 hours indicated that approximately 2.5 days must elapse to achieve steady-state concentrations of cyproheptadine after oral administration of multiple doses. A 12-hour dosing interval is acceptable, but an 8-hour interval may be indicated for some cats.

Clinical Relevance

On the basis of pharmacokinetic parameters determined in this study, the oral form of cyproheptadine appears to be suitable for use in clinical trials to treat anorexia in cats. Its half-life is compatible with once or twice daily dosing. (Am J Vet Res 1998;59:79–81)

Free access
in American Journal of Veterinary Research