Objective-To compare the urodynamic and hemodynamic effects of different dosages of phenylpropanolamine and ephedrine and determine effective dosages in increasing urethral resistance in female dogs. Animals-20 sexually intact female Beagles. Procedure-Dogs were allocated into 4 groups and received phenylpropanolamine once, twice, or 3 times daily, or ephedrine twice daily, for 14 days. On days 0, 7, and 14, urethral pressure profiles were performed while dogs were anesthetized with propofol. Variables recorded included maximum urethral pressure, maximum urethral closure pressure, integrated pressure, functional profile length, anatomic profile length, plateau distance, distance before maximum urethral pressure, and maximum meatus pressure. Arterial and central venous pressures were measured before anesthetic induction and 10 and 35 minutes after induction. Results-Administration of phenylpropanolamine once daily or ephedrine twice daily significantly increased maximum urethral pressure and maximum urethral closure pressure. Values for integrated pressure were significantly increased after 14 days of once-daily administration of phenylpropanolamine. Variables did not change significantly from day 7 to day 14. Diastolic and mean arterial blood pressures increased significantly during the treatment periods, and arterial pressure decreased during propofol infusion. Conclusions and Clinical Relevance-Oral administration of phenylpropanolamine once daily or ephedrine twice daily increased urethral resistance in clinically normal dogs and may be recommended for management of urethral sphincter mechanism incompetence. Treatment efficacy may be assessed after 1 week. Dogs with concurrent cardiovascular disease should be monitored for blood pressure while receiving alpha-adrenergic agents because of the effects on diastolic and mean arterial pressure.

Objective-To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. Animals-6 adult horses. Procedures-Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. Results-Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 +/- 18.41%. The elimination half-life after a single orally administered dose was 13.11 +/- 2.85 hours, and the maximum plasma concentration was 2.43 +/- 0.4 microgram/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study. Conclusions and Clinical Relevance-Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration less than or equal to 1 microgram/mL. Because of the possible nonlinearity of this drug as well as the potential for accumulation, chronic dosing studies and clinical trials are needed to determine the appropriate dosing regimen for voriconazole in horses.

Objectives-To determine effects of commonly used diuretic treatments on glomerular filtration rate (GFR), renal blood flow (RBF), and urine output (UO) and compare 2 methods of GFR measurement in healthy awake cats. Animals-8 healthy cats. Procedure-In a randomized crossover design, cats were randomly allocated to 4 groups: control; IV administration of fluids; IV administration of fluids and mannitol; and IV administration of fluids, dopamine, and furosemide. Inulin and para-aminohippuric acid were used for determination of plasma clearance for GFR and RBF, respectively. Plasma clearance of technetium-Tc-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) was also used for GFR determination. Results-Furosernide-dopamine induced the largest UO, compared with other groups. Both mannitol and fluid therapy increased RBF, compared with the control group. Mannitol, and not fluid therapy, increased RBF, compared with furosemide-dopamine. There were significant differences in GFR values calculated from 99mTc-DTPA and inulin clearances between the 2 groups. In all groups, use of 99mTc-DTPA caused underestimation of GFR, compared with use of inulin. Conclusions and Clinical Relevance-In healthy awake cats, administration of furosemide-dopamine did not increase GFR or RBF despite increased UO. Fluid therapy and fluid therapy plus mannitol improved RBF. Determination of GFR by use of 99mTc-DTPA cannot always be substituted for inulin clearance when accurate measurement is required.

Objective-To evaluate the effects of morphine administration for 6 days on gastrointestinal tract function in healthy adult horses. Animals-5 horses. Procedures-Horses were randomly allocated into 2 groups in a crossover study. Horses in the treatment group received morphine sulfate at a dosage of 0.5 mg/kg, IV, every 12 hours for 6 days. Horses in the control group received saline (0.9% NaCl) solution at a dosage of 10 mL, IV, every 12 hours for 6 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (evaluated by use of barium-filled spheres and radiographic detection in feces), fecal moisture content, borborygmus score, and signs of CNS excitement and colic. Results-Administration of morphine resulted in gastrointestinal tract dysfunction for 6 hours after each injection. During those 6 hours, mean +/- SD defecation frequency decreased from 3.1 +/- 1 bowel movements in control horses to 0.9 +/- 0.5 bowel movements in treated horses, weight of feces decreased from 4.1 +/- 0.7 kg to 1.1 +/- 0.7 kg, fecal moisture content decreased from 76 +/- 2.7% to 73.5 +/- 2.9%, and borborygmus score decreased from 13.2 +/- 2.9 to 6.3 +/- 3.9. Mean gastrointestinal transit time was also increased, compared with transit times in control horses. Conclusions and Clinical Relevance-Morphine administered at 0.5 mg/kg twice daily decreased propulsive motility and moisture content in the gastrointestinal tract lumen. These effects may predispose treated horses to development of ileus and constipation.

Objective-To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species. Animals-5 clinically normal horses and 5 clinically normal donkeys. Procedures-Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinetic variables. Results-In horses and donkeys, mean +/- SD area under the curve was 18.8 +/- 7.31 microgram/mL/h and 4.6 +/- 2.55 microgram/mL/h, respectively; mean residence time (MRT) was 9.6 +/- 9.24 hours and 0.6 +/- 0.36 hours, respectively. Total body clearance (CL(T)) was 34.7 +/- 9.21 mL/kg/h in horses and 187.9 +/- 147.26 mL/kg/h in donkeys. Volume of distribution at steady state (VD(SS)) was 270 +/- 160.5 mL/kg in horses and 93.2 +/- 33.74 mL/kg in donkeys. All values, except VD(SS), were significantly different between donkeys and horses. Conclusions and Clinical Relevance-The small VD(SS) of meloxicam in horses and donkeys (attributed to high protein binding) was similar to values determined for other nonsteroidal anti-inflammatory drugs. Compared with other species, horses had a much shorter MRT and greater CL(T) for meloxicam, indicating a rapid elimination of the drug from plasma; the even shorter MRT and greater CL(T) of meloxicam in donkeys, compared with horses, may make the use of the drug in this species impractical.

Objective-To determine the pharmacokinetics of methylprednisolone (MP) and develop a pharmacokinetic-pharmacodynamic model of the related changes in plasma concentrations of endogenous hydrocortisone (HYD) and cortisone (COR) following intra-articular administration of methylprednisolone acetate (MPA) in horses. Animals-6 Thoroughbreds. Procedures-In each horse, 200 mg of MPA was injected intrasynovially into a carpal joint, and plasma MP, HYD, and COR concentrations were determined via liquid chromatography-mass spectrometry. Results-A 5-compartment pharmacokinetic-pharmacodynamic model was used to describe the concatenated changes in the plasma concentrations of MP, HYD, and COR and to estimate the instantaneous rate of endogenous HYD production. The median transfer half-life (t(1/2t)) of methylprednisolone from the joint to plasma and elimination half-life (t(1/2e)) from plasma were 1.7 and 19.2 hours, respectively. Maximum plasma concentration of methylprednisolone was 7.26 +/- 3.3 ng/mL at 8 hours, which decreased to 0.11 +/- 0.08 ng/mL at 144 hours after injection. At 3 hours after MPA administration, plasma COR and HYD concentrations were significantly decreased from baseline values (from 2.9 +/- 0.28 ng/mL to 2.10 +/- 1.0 ng/mL and from 61.1 +/- 18.9 ng/mL to 25.7 +/- 12.1 ng/mL, respectively). Conclusions and Clinical Relevance-The sensitivity of the analytic method used allowed complete description of the related kinetics of MP, HYD, and COR following intra-articular administration of MPA. A single intra-articular administration of MPA profoundly affected the secretion of HYD and COR in horses; secretion of endogenous corticosteroids remained suppressed for as long as 240 hours after injection.

Objective-To use in vitro assays to evaluate the effects of a novel immunosuppressive agent, FTY720, on biological functions (migration, phagocytosis, and production of reactive-oxygen species ROS) of feline peripheral neutrophils and determine the cytotoxic effects of FTY720 on feline peripheral neutrophils. Sample Population-Peripheral neutrophils obtained from 8 healthy cats. Procedure-Peripheral neutrophils were isolated from blood samples obtained from the 8 cats and exposed to the phosphorylated form of FTY720 (FTY720-P). A fluorescence-based in vitro evaluation of migration was performed. Phagocytosis of microbes and production of ROS were evaluated by use of a 2-color flow cytometry system. Samples of whole blood obtained from the cats were incubated with various concentrations of FTY720-P, fluorescein-labeled Staphylococcus aureus, and dihydroethidium. Cytotoxic effects were evaluated by use of propidium iodide staining. Results-Addition of FTY720-P caused a slight nonsignificant decrease in phagocytosis and production of ROS by feline peripheral neutrophils. Migration activity of feline peripheral neutrophils was significantly increased by the addition of FTY720-P. Addition of FTY720-P at concentrations considered for clinical use did not increase the death rate of feline peripheral neutrophils. Conclusions and Clinical Relevance-FTY720 does not inhibit critical functions of feline peripheral neutrophils in vitro.

pharmacokinetics of [3H]levamisole in pigs after oral and intramuscular administration

Two of 3 groups of Holstein-Friesian steers (groups II and III; n = 5 each) were fed a ration containing corn naturally contaminated with 800 ng of aflatoxin/g. The other group of steers (group I; n = 5) was fed a ration containing noncontaminated corn. The respective rations were fed for 17.5 weeks, except the ration given to group III; the latter's first diet (contaminated with aflatoxin) was changed to a noncontaminated diet after 15 weeks, continuing for the remaining 2.5 weeks. All steers were killed and tissues and fluids were obtained for aflatoxin analysis. Although aflatoxin B1 and M1 could be detected in blood and urine at several sampling times during the experimental period in groups II and III steers (given the diets containing aflatoxin), there appeared to be no effects on body weight gains and immune phenomena, such as lymphoblastogenesis and antibody production, but there was a waning of the delayed cutaneous hypersensitivity in steers given aflatoxin-contaminated diets. In group III animals (diet was changed to noncontaminated ration at 15 weeks), aflatoxin B1 and M1 disappeared from urine before they were slaughtered. All tissues and fluids, except the rumen contents from these group III steers, were void of detectable aflatoxins B1 and M1 at necropsy. The concentrations of aflatoxin B1 in the rumen content of the latter steers were low. All tissues collected at necropsy from the group II steers fed the aflatoxin diet throughout the 17.5 weeks had detectable aflatoxins B1 or M1 present.

Surface temperatures of hoofs of calves given toxic anion fractions of tall fescue were measured with an infrared sensitive camera. These changes expressed in terms of a weighted average coronary band temperature relate to clinical signs of fescue foot. The weighted average coronary band temperature values for control calves given saline solution were 27 to 31 C; those values of test calves given anion fractions of tall fescue were as low as 22 +/- 1 C. Videothermometry provides an independent, permanent, objective measure that is useful in assessing fescue-foot potential of tall fescue fractions by intraperitoneal injection. Videothermometry may also serve as a clinical means for determining progression of the total fescue foot syndrome.