We evaluated the efficacy of buparvaquone in eliminating infection with Babesia equi of European origin in carrier horses and in splenectomized horses with experimentally induced acute infection. When administered at the rate of 5 mg/kg of body weight, IV, 4 times at 48-hour intervals, buparvaquone prompted rapid abatement of parasitemia. However, secondary and tertiary recrudescent parasitemias invariably returned with establishment of the carrier state. Buparvaquone, at the dosage evaluated, had transitory therapeutic efficacy against acute B equi infection in splenectomized horses, but was unable alone to clear carrier infection.

Four hours prior to exercise on a high-speed treadmill, 4 dosages of furosemide (0.25, 0.50, 1.0, and 2.0 mg/kg of body weight) and a control treatment (10 ml of 0.9% NaCl) were administered IV to 6 horses. Carotid arterial pressure (CAP), pulmonary arterial pressure (PAP), and heart rate were not different in resting horses before and 4 hours after furosemide administration. Furosemide at dosage of 2 mg/kg reduced resting right atrial pressure (RAP) 4 hours after furosemide injection. During exercise, increases in treadmill speed were associated with increases in RAP, CAP, PAP, and heart rate. Furosemide (0.25 to 2 mg/kg), administered 4 hours before exercise, reduced RAP and PAP during exercise in dose-dependent manner, but did not influence heart rate. Mean CAP was reduced by the 2-mg/kg furosemide dosage during exercise at 9 and 11 m/s, but not at 13 m/s. During recovery, only PAP was decreased by furosemide administration. Plasma lactate concentration was not significantly influenced by furosemide administration. Furosemide did not influence PCV or hemoglobin concentration at rest prior to exercise, but did increase both variables in dose-dependent manner during exercise and recovery. However, the magnitude of the changes in PCV and hemoglobin concentration were small in comparison with changes in RAP and PAP, and indicate that furosemide has other properties in addition to its diuretic activities. Furosemide may mediate some of its cardiopulmonary effects by vasodilatory activities that directly lower pulmonary arterial pressure, but also increase venous capacitance, thereby reducing venous return to the atria and cardiac filling.

The bioavailability and pharmacokinetics of ibuprofen, a nonsteroidal antiinflammatory drug, was studied in healthy Shetland ponies. Ibuprofen was administered IV, as a suspension, and as a solid solution oral paste to ponies from which food was withheld. The suspension paste was also administered to ponies that received hay and water ad libitum. Both formulations had an absolute bioavailability of about 80%. Bioavailability was not influenced by feeding.

Ten foals of various breeds were deprived of colostrum from birth to 36 hours of age, then were allotted to 2 groups. Foals of group 1 (n = 6) were given 20 g (200 ml) of purified equine IgG IV in a 10% solution, and foals of group 2 (n = 4) were given 30 g (300 ml) of the same preparation. Total administration time for each 10 g of IgG in 100 ml was approximately 10 minutes. Serum IgG concentration in foals was assessed prior to, between 24 and 48 hours, and at 7 and 14 days after IgG administration. Between 24 and 48 hours after IgG administration, mean serum IgG concentration in group-1 foals was 425 mg/dl (range, 350 to 480 mg/dl). Mean body weight for this group of foals was 50.3 kg (range, 43.3 to 54.7 kg). For group-2 foals, mean serum IgG concentration was 768 mg/dl (range, 640 to 920 mg/dl) between 24 and 48 hours after administration of IgG. Foals of this group had mean body weight of 43.2 kg (range, 36.5 to 47.5 kg). Serum IgG concentration in group-2 foals at 24 to 48 hours was significantly (P = 0.005) greater than that in group-1 foals. Mean total IgG recovery at 24 to 48 hours, calculated on the basis of 94.5 ml of plasma volume/kg of body weight, was approximately 100%. Values of IgG measured in all foals 1 and 2 weeks after administration of the IgG concentrate were equivalent to values expected after normal decay of passively acquired IgG. Mild, adverse reactions occurred in 3 of the treated (1 group-1 foal and 2 group-2 foals).

The effects of single IV injections of sodium bicarbonate (0.5 mEq/kg of body weight, 1 mEq/kg, 2 mEq/kg, and 4 mEq/kg) on serum osmolality, serum sodium, chloride, and potassium concentrations, and venous blood gas tensions in 6 healthy cats were monitored for 180 minutes. Serum osmolality increased and remained significantly (P less than 0.05) increased for 120 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium was increased significantly (P less than 0.05) for 30 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium decreased and remained significantly (P less than 0.05) decreased for 120 minutes in cats given 1 g of 20% mannitol/kg, and serum osmolality was significantly (P less than 0.05) decreased at 30 and 60 minutes. Serum chloride decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and was significantly decreased for 30 minutes in cats given 2 mEq and 4 mEq of sodium bicarbonate/kg. Serum chloride decreased and remained significantly (P less than 0.05) decreased for 30 minutes in cats given 1 g of 20% mannitol/kg. Serum sodium and serum osmolality did not change significantly (P less than 0.05) in cats given 4 ml of 0.9% sodium chloride/kg. Serum potassium decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and for 120 minutes in cats given 2 mEq/kg or 4 mEq/kg. There was a significantly (P less than 0.05) greater decrease in serum potassium that lasted for 30 minutes after giving sodium bicarbonate at the dosage of 4 mEq/kg, compared with other dosages given. Serum potassium did not change significantly in cats given 1 g of 20% mannitol/kg, but was significantly (P less than 0.05) decreased 10 minutes following 4 ml of 0.9% sodium chloride/kg. Sodium bicarbonate infusion significantly (P less than 0.05) increased venous blood pH and plasma bicarbonate concentration in all cats. The magnitude and duration of these changes were significantly greater following administration of sodium bicarbonate at dosages of 2 mEq/kg and 4 mEq/kg. Significant (P less than 0.05) increases in PCO2 were associated only with the highest dosage of sodium bicarbonate (4 mEq/kg). Base excess increased significantly (P less than 0.05) in all cats following sodium bicarbonate infusion. There were significantly (P less than 0.05) greater increases in base excess lasting 30 minutes following administration of sodium bicarbonate at dosages of 2 mEq/kg and 4 mEq/kg. Significant (P less than 0.05) changes in venous blood pH, PCO2, or bicarbonate were not observed in cats given 4 ml of 0.9% sodium chloride/kg, or in cats given 1 g of 20% mannitol/kg. Base excess was significantly (P less than 0.05) increased for 10 minutes in cats given 1 g of 20% mannitol/kg. As expected, 4 mEq of sodium bicarbonate/kg induced the most time- and dosage-related effects. Caution should be used when administering sodium bicarbonate IV to cats at dosages greater than 2 mEq/kg, because of the potential for important acid-base and electrolyte changes.

The effect of age on the pharmacokinetics of chloramphenicol was determined after IV administration of chloramphenicol sodium succinate (25 mg/kg of body weight) to 6 foals at 1 day and 3, 7, 14, and 42 days of age. The disposition of chloramphenicol was best described, using a two-compartment open model in all foals at all ages evaluated. Significant age-related changes were observed in values for the major kinetic terms describing the disposition of chloramphenicol in foals; the greatest changes were observed between 1 day and 3 days of age. The mean +/- SD value for elimination rate constant (beta) for chloramphenicol in 1-day-old foals (0.131 +/- 0.06 h-1) was significantly (P < 0.005) lower than the value in 3-day-old foals (0.514 +/- 0.156 h-1), and both values were significantly (P < 0.005) lower than values for beta in 7-, 14-, and 42-day-old foals. With increasing age, the increase in the mean value for beta resulted in decrease in the harmonic mean elimination half-time (t1/2 beta) for chloramphenicol, from 5.29 hours in 1-day-old foals to: 1.35 hours in 3-day-old foals; 0.61 hour in 7-day-old foals; 0.51 hour in 14-day-old foals; and 0.34 hour in 42-day-old foals. At 1, 3, and 7 days of age, values for t1/2 beta of chloramphenicol in a premature foal born after parturition was induced with oxytocin, were considerably longer than comparable t1/2 beta values for term foals born naturally. The mean body clearance (ClB) of chloramphenicol in 1-day-old foals (2.25 +/- 0.67 ml/min.kg of body weight) was significantly lower than values in: 3-day-old (6.23 +/- 2.22 ml/min.kg; P < 0.05); 7-day-old (8.86 +/- 1.90 ml/min.kg; P < 0.0005); 14-day-old (9.63 +/- 1.63 ml/min.kg; P < 0.0005); and 42-day-old (9.68 +/- 2.76 ml/min.kg; P < 0.0001) foals. In foals of all ages, ClB of chloramphenicol in the parturition-induced premature foal was lower than the mean value for term foals born naturally. The volume of distribution (V'd[area]) of chloramphenicol decreased progressively with increasing age between day 1 and day 42, so that the mean value for 42-day-old foals (362 +/- 163 ml/kg) was less than a third the mean value for 1-day-old foals (1,101 +/- 284 ml/kg). The mean value for V'd(area) in 1-day-old foals was significantly greater than values for: 7-day-old (491 +/- 158 ml/kg; P < 0.01); 14-day-old (426 +/- 65 ml/kg; P < 0.005); and 42-day-old (362 +/- 162; P < 0.0005) foals, and the mean value for V'd(area) on day 3 was significantly (P < 0.05) greater than the mean value for V'd(area) on days 7, 14, and 42. Using dosage calculations based on mean values for the pharmacokinetic terms derived for each age group, it was predicted that to maintain plasma chloramphenicol concentration > 8 microgram/ml, chloramphenicol sodium succinate (25 mg/kg) would have to be administered at dose intervals of 10, 3, 1.5, 1.5, and 1 hours in clinically normal foals 1 day and 3, 7, 14, and 42 days, of age, respectively. It was concluded that the marked changes in the disposition of chloramphenicol detectable during the first few days of life, the variation between individuals, the potentially major effect of prematurity, and the potential for compromised liver function in septicemic foals indicate that use of drugs, such as chloramphenicol, which rely heavily on hepatic metabolic processes for elimination, should be avoided whenever possible during the early neonatal period, unless plasma concentration is monitored.

During the first part of a study, cats were inoculated with Cryptococcus neoformans via the following routes: intradermal, intranasal, IV, and intracisternal. Only use of the IV route of inoculation consistently induced disseminated cryptococcosis. In the second part of the study, disseminated cryptococcosis was experimentally induced in cats via IV inoculation of C neoformans. One month after inoculation, 3 cats were treated with ketoconazole (10 mg/kg of body weight/d) and 3 cats were treated with itraconazole (10 mg/kg/d) for 3 months. One of the ketoconzole-treated and 2 of the itraconazole-treated cats also had cryptococcosis of the CNS when treatment was begun. During treatment, serum cryptococcal antigen titer progressively decreased in all cats. Abnormalities in CBC values or the serum biochemical profile were not found in any cat during treatment. However, all ketoconazole-treated cats became anorectic and lost weight. Side effects were not seen in itraconazole-treated cats. During the 3-month posttreatment observation period, all cats remained healthy. At necropsy, histologic evidence of cryptococcosis was not found in the 3 ketoconazole-treated cats or in 2 of the itraconazole-treated cats. In the third itraconazole-treated cat, cryptococcal organisms were found in the kidneys.

The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single IV and IM doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After IV administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of > 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, harmonic mean = 3.14 hours). Mean +/- SD clearance after IV administration was 2.51 +/- 0.96 ml/kg/min. After IM administration, the harmonic mean for the elimination phase (t1/2 beta) was prolonged at 5.20 hours. Bioavailability after IM dosing gave a mean +/- SD (n = 5) of 76.0 +/- 28.0%. Adult lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first IV, remainder IM) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 microgram/ml at 2 hours after each dosing and 0.5 microgram/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study. Flunixin concentrations necessary to induce therapeutic effects in cattle are unknown. Results of our study indicate that administration of 1.1 mg/kg doses of flunixin meglumine at 8-hour intervals would produce plasma concentrations similar to those demonstrated to be effective clinically in treatment of equine musculoskeletal disorders and colic.

OBJECTIVE To evaluate physical compatibility of small animal (SAE) and large animal (LAE) injectable formulations of enrofloxacin with select IV fluids and drugs. SAMPLE 162 admixtures containing SAE or LAE with saline (0.9% NaCl) solution, lactated Ringer solution (LRS), Plasma-Lyte A (PLA), 6% hydroxyethylstarch 130/0.4 (HES), metoclopramide, or ampicillin-sulbactam. PROCEDURES In the first of 2 simultaneously conducted experiments, admixtures containing enrofloxacin (10 mg/kg) and a volume of IV fluid that would be administered over a 20-minute period when dosed at the maintenance infusion rate (40 mL/kg/d for saline solution, LRS, and PLA and 20 mL/kg/d for HES) were created. In the second experiment, enrofloxacin (10 mg/kg) was admixed with saline solution (40 mL/kg/d) and metoclopramide (2 mg/kg/d) or ampicillin-sulbactam (30 mg/kg). In both experiments, admixture components were infused into a flask over 20 minutes assuming patient weights of 5, 10, and 20 kg. Admixtures were created by use of undiluted SAE and SAE diluted 1:1 with saline solution and undiluted LAE and LAE diluted 1:1 and 1:10 with saline solution. Admixtures were assessed for physical incompatibility at 0, 15, 30, and 60 minutes after completion of mixing. Physical incompatibility was defined as gross precipitation, cloudiness, Tyndall effect, or change in turbidity. RESULTS Admixtures containing undiluted SAE or LAE were physically incompatible with saline solution, PLA, LRS, and HES. Because saline solution was used to dilute SAE and LAE, all admixtures containing diluted SAE or LAE were also physically incompatible. Physical compatibility of enrofloxacin with metoclopramide or ampicillin-sulbactam could not be assessed because those admixtures also contained saline solution. CONCLUSIONS AND CLINICAL RELEVANCE Enrofloxacin was physically incompatible with all tested solutions.

OBJECTIVE To describe the pharmacokinetics of morphine, lidocaine, and ketamine associated with IV administration of a constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination to calves undergoing umbilical herniorrhaphy. ANIMALS 20 weaned Holstein calves with umbilical hernias. PROCEDURES Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 μg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). For all calves, the CRI was begun after anesthesia induction. Blood samples were obtained immediately before and at predetermined times for 120 hours after initiation of the assigned treatment. Noncompartmental analysis was used to estimate pharmacokinetic parameters for the MLK group. RESULTS During the CRI, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine. Mean terminal half-life was 4.1, 0.98, and 1.55 hours and area under the concentration-time curve was 41, 14,494, and 7,426 h•μg/mL for morphine, lidocaine, and ketamine, respectively. After the CRI, the mean serum drug concentration at steady state was 6.3, 616.7, and 328 ng/mL for morphine, lidocaine, and ketamine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE During the CRI of the MLK solution, steady-state serum concentrations were achieved for lidocaine and ketamine, but not morphine, likely owing to the fairly long half-life of morphine. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols.