Disposition of levetiracetam in healthy adult horses.

Nine horses received 20 mg/kg of intravenous (LEVIV ); 30 mg/kg of intragastric, crushed immediate release (LEVCIR ); and 30 mg/kg of intragastric, crushed extended release (LEVCER ) levetiracetam, in a three-way randomized crossover design. Crushed tablets were dissolved in water and administered by nasogastric tube. Serum samples were collected over 48 hr, and levetiracetam concentrations were determined by immunoassay. Mean ± SD peak concentrations for LEVCIR and LEVCER were 50.72 ± 10.60 and 53.58 ± 15.94 µg/ml, respectively. The y-intercept for IV administration was 64.54 ± 24.99 µg/ml. The terminal half-life was 6.38 ± 1.97, 7.07 ± 1.93 and 6.22 ± 1.35 hr for LEVCIR , LEVCER, and LEVIV , respectively. Volume of distribution at steady-state was 630 ± 73.4 ml/kg. Total body clearance after IV administration was 74.40 ± 19.20 ml kg-1  hr-1 . Bioavailability was 96 ± 10, and 98 ± 13% for LEVCIR and LEVCER , respectively. A single dose of Levetiracetam (LEV) was well tolerated. Based on this study, a recommended dosing regimen of intravenous or oral LEV of 32 mg/kg every 12 hr is likely to achieve and maintain plasma concentrations within the therapeutic range suggested for humans, with optimal kinetics throughout the dosing interval in healthy adult horses. Repeated dosing and pharmacodynamic studies are warranted.

Evaluation of transdermal fentanyl patches for analgesia in cats undergoing onychectomy.

OBJECTIVE: To evaluate efficacy and safety of using transdermal fentanyl patches (TFP) for analgesia in cats undergoing onychectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 45 client-owned cats weighing > or = 2.7 kg (5.9 lb) undergoing onychectomy, onychectomy and ovariohysterectomy, or onychectomy and castration. PROCEDURE: Cats were randomly assigned to be treated with a TFP (25 micrograms/h) or butorphanol; TFP were applied a minimum of 4 hours before surgery (approx 8 hours prior to extubation). Rectal temperature, heart rate, respiratory rate, force applied by the forelimbs, and serum fentanyl concentration were measured, and temperament, recovery, degree of sedation, severity of pain, severity of lameness, and appetite were scored before and periodically for up to 40 hours after surgery. RESULTS: Cats treated with a TFP had better recovery scores at 2 of 4 evaluation times, lower sedation scores at 2 of 8 evaluation times, and lower pain scores at 6 of 8 evaluation times, compared with cats treated with butorphanol. Use of a pressure-sensitive mat to evaluate force applied by the forelimbs did not reveal any differences between groups but did reveal a significant difference between preoperative and postoperative values. Mean +/- SD serum fentanyl concentrations were 1.56 +/- 1.08, 4.85 +/- 2.38, 4.87 +/- 1.56, and 4.35 +/- 2.97 ng/ml approximately 8, 24, 32, and 48 hours, respectively, after TFP placement. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of a TFP (25 micrograms/h) for postoperative analgesia in cats undergoing onychectomy with or without surgical sterilization is safe and effective.

A canine model of multiple portosystemic shunting.

The objective of this study was to develop and describe an experimental canine model of multiple acquired portosystemic shunts (PSS) similar in nature to spontaneously occurring PSS. Sixteen dogs were used and were divided into a control (n = 6) and a diseased group (n = 10). Dogs of the diseased group were administered dimethylnitrosamine (2 mg/kg of body weight, po) twice weekly, and clinicopathologic, ultrasonographic, and hepatic scintigraphic findings were recorded during the development of hepatic disease and PSS. Surgery was then performed to permit visual verification of multiple shunts, catheter placement for portography examination, and biopsy of the liver. All diseased dogs developed severe hepatic disease and multiple PSS as documented visually at surgery and on portography. Based on this study, dimethylnitrosamine-induced portosystemic shunting appears to be an appropriate model for spontaneously occurring multiple PSS secondary to portal hypertension.

Detection of portal and systemic bacteremia in dogs with severe induced hepatic disease and multiple portosystemic shunts.

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 < or = 0.01) and significantly lower percentage of gram-negative bacteria (58% of positive culture results, P < or = 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. CONCLUSION: Portal and systemic, predominantly gram-negative, bacteremia is present in catheterized, clinically normal dogs and dogs with dimethylnitrosamine-induced hepatic disease and multiple PSS.

Drugs acting on blood and/or blood forming organs.

Pharmacologic therapy for anemia is oriented toward (1) providing components needed for red blood cell production (vitamin B12 and folic acid), including hemoglobin synthesis (iron and other minerals), and (2) stimulating bone marrow formation of red blood cells. Drugs used to stimulate bone marrow activity will be the focus of this article.

Concentration of enrofloxacin and its active metabolite in alveolar macrophages and pulmonary epithelial lining fluid of dogs.

The purpose of this study was to determine the concentration of enrofloxacin and its active metabolite, ciprofloxacin, in alveolar macrophages (AM) and epithelial lining fluid (ELF) of the lungs in comparison to plasma concentrations in healthy dogs. Eleven dogs were given a single oral dose (5 mg/kg) of enrofloxacin. Four hours later, plasma and bronchoalveolar lavage (BAL) fluid were collected. Cells were separated from the BAL fluid and lysed for determination of drug concentrations within AM. Supernatant was used to determine concentrations of drugs in ELF. Drug assays were performed by high-performance liquid chromatography. The concentration of enrofloxacin (mean +/- SD) was 0.33 +/- 0.14 microgram/mL in plasma, 3.34 +/- 2.4 micrograms/mL in AM and 4.79 +/- 5.0 micrograms/mL in ELF. The concentration of ciprofloxacin was 0.42 +/- 0.26 microgram/mL in plasma, 1.15 +/- 1.03 micrograms/mL in AM and 0.26 +/- 0.26 microgram/mL in ELF. Mean concentrations of both drugs in AM were greater than in plasma (AM to plasma ratio, 10.3 for enrofloxacin and 4.7 for ciprofloxacin). Mean concentrations of enrofloxacin, but not ciprofloxacin, in ELF were greater than in plasma (ELF to plasma ratio, 13.5 for enrofloxacin and 0.52 for ciprofloxacin). Enrofloxacin concentrations in AM and ELF largely exceeded the MICs of the major bacterial pathogens and surpassed by about two times the breakpoint MIC of that drug, and ciprofloxacin concentrations in AM surpassed the MIC of many susceptible organisms. These results suggest that sufficient antimicrobial activity is present in AM and ELF of dogs following oral administration of enrofloxacin to be effective in the treatment of lower respiratory tract infections involving susceptible organisms.

Endotoxemia associated with experimentally induced multiple portosystemic shunts in dogs.

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 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 < or = 0.0002), hepatic vein (P < or = 0.0001), and caudal vena cava (P < or = 0.0004) than did control dogs. With respect to time, endotoxin presence was greater in the diseased group before banding (P < or = 0.0002), and at 20 (P < or = 0.0008), 40 (P < or = 0.002), 60 (P < or = 0.006), and 120 (P < or = 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.

Use of hepatobiliary scintigraphy in the diagnosis of extrahepatic biliary obstruction in dogs and cats: 25 cases (1982-1989).

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.

Drug therapy in cats: a therapeutic category approach.

The third article of this 4-part series discusses drug therapy in cats by therapeutic category. Specifically, the use of drugs to control infections, pain, fever, inflammation, cancer, and selected parasites is described. In addition, the use of hormonally related drugs and selected miscellaneous drugs in cats is addressed. Drugs emphasized are those for which use in cats is frequently associated with adverse reactions or drugs for which use is limited to illnesses that tend to be unique in cats.