Multicenter randomized prospective clinical evaluation of meloxicam administered via transmucosal oral spray in client-owned dogs.

The clinical safety and efficacy of a transmucosal oral spray (TMOS) formulation of meloxicam was evaluated for the control of pain and inflammation associated with osteoarthritis in dogs. A total of 280 client-owned dogs were enrolled at fourteen veterinary clinics: there were 187 dogs in the meloxicam TMOS group and 93 in the placebo control group. Dogs received placebo or treatment spray once daily for twenty-eight days. Improvement in signs of osteoarthritis was measured using client-specific outcome measures (CSOM) made at days 14 and 28 and veterinary assessments of lameness and pain on palpation made at day 28. A significantly higher number of dogs in the meloxicam TMOS group were treatment successes at 28 days (72.6%) compared with the placebo group (46.9%), based on CSOM scores. Total CSOM scores were significantly lower in the meloxicam TMOS-treated group compared with the placebo group at both 14 and 28 days. Differences between treatment groups were not observed in veterinary assessments. Gastrointestinal effects of meloxicam were observed in some animals. Meloxicam TMOS was found to be safe and effective in dogs for the control of pain and inflammation associated with osteoarthritis.

Evaluation of progesterone treatment to create a model for equine endometritis.

To investigate a model for equine endometritis, 12 mares with normal reproductive tracts were divided into 2 groups. All mares received progesterone in oil, 250 mg im, daily. At 5 days after initiation of progesterone administration, the uteri were inoculated with 10(6) colony forming units of Pseudomonas aeruginosa. The day of inoculation was designated Day 0. On Day 6, endometrial swab samples yielded P. aeruginosa in 5 mares; samples from the other 7 mares yielded heavy growth of Escherichia coli, Streptococcus zooepidemicus, Klebsiella pneumoniae, Enterobacter spp., Citrobacter diversus, Staphylococcus epidermidis and Streptococcus morbillorum. On Days 6, 7 and 8, Group A mares received intrauterine infusions of 6 g ticarcillin disodium and 0.2 g clavulanate potassium in 100 ml sterile saline. Group B mares received infusions of saline only. The incidence of swab specimens yielding no bacterial growth was significantly higher in Group A than Group B mares on Days 8 and 13 (4/6 vs 0/6). Swab samples from 5 of the 6 mares in Group A yielded growth of fungi on Days 13 and 19. Mares in Group B were then similarly treated with ticarcillin/clavulanate infusions, on Days 19, 20 and 21. The incidence of swab specimens yielding no bacterial growth was 2/6 and 1/6 on Days 21 and 26, respectively; fungi were not recovered from these mares at any time. The incidence of no-growth swabs after antibiotic treatment tended to be higher in Group A and incidence of fungal recovery after antibiotic treatment was significantly higher in Group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Concentrations of amino acids in the plasma of neonatal foals with septicemia.

Concentrations of amino acids in the plasma of 13 neonatal foals with septicemia were compared with the concentrations of amino acids in the plasma of 13 age-matched neonatal foals without septicemia. Analysis of the results revealed significantly lower concentrations of arginine, citrulline, isoleucine, proline, threonine, and valine in the plasma of foals with septicemia. The ratio of the plasma concentrations of the branched chain amino acids (isoleucine, leucine, and valine) to the aromatic amino acids (phenylalanine and tyrosine), was also significantly lower in the foals with septicemia. In addition, the concentrations of alanine, glycine, and phenylalanine were significantly higher in the plasma of foals with septicemia. Therefore, neonatal foals with septicemia had significant differences in the concentrations of several amino acids in their plasma, compared with concentrations from healthy foals. These differences were compatible with protein calorie inadequacy and may be related to an alteration in the intake, production, use, or clearance of amino acids from the plasma pool in sepsis.

Effect of age on the concentrations of amino acids in the plasma of healthy foals.

The concentrations of 23 amino acids in the plasma of 13 healthy foals were determined before suckling, when foals were 1 to 2 days old, 5 to 7 days old, 12 to 14 days old, and 26 to 28 days old. The ratio of the branched chain amino acids to the aromatic amino acids was also calculated at the 5 time points. Analysis of the concentrations at the 5 ages revealed a significant temporal relationship for each amino acid ranging from a polynomial order of 1 to 4 inclusively. There were significant differences between several concentrations of amino acids in plasma at specific sample times; however, no consistent patterns were revealed. The concentrations of amino acids in healthy foals were markedly different from previously determined values in adult horses. The significant differences in the concentrations of amino acids in plasma of healthy foals at the 5 ages may represent developmental aspects of amino acid metabolism or nutrition.

Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration.

The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age. After i.v. administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two-compartment open model. Mean plasma elimination-rate constant (beta) and clearance (ClB) for ticarcillin were significantly less (P less than 0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P less than 0.05), in the foals at 3 days compared with 28 days of age. This indicated that renal excretion mechanisms were immature and ticarcillin was more widely distributed in 3-day-old foals. The mean elimination rate constant for clavulanate was significantly less (P less than 0.01) at 3 days than at 28 days of age. Values of the major kinetic terms describing the disposition of ticarcillin after i.m. administration to five 3-day-old foals were not significantly different from values of these parameters in the same foals at 28 days of age. After i.m. administration of the drug combination, plasma clavulanate concentrations peaked significantly later (P less than 0.01), and the elimination-rate constant (kd) for clavulanate was significantly less (P less than 0.01), in 3-day-old foals than in 28-day-old foals. The bioavailabilities of ticarcillin and clavulanate after i.m. administration in 3-day-old foals were 100% and 88.3%, respectively, and in 28-day-old foals were 100% and 27.4%, respectively. Mean plasma ticarcillin concentrations exceeded 16 micrograms/ml for a longer period after i.m. administration of the drug combination than after i.v. administration to foals of both age groups. By virtue of the frequency of administration required and the painful response elicited by i.m. injection, it is recommended that when the combination of ticarcillin disodium (50 mg/kg) and clavulanate potassium (1.67 mg/kg) is used in foals to treat infections caused by susceptible organisms (MIC less than or equal to 16 micrograms/ml), it should be administered i.v. four times daily.

Preliminary investigation of alterations in blood viscosity, cellular composition, and electrophoresis plasma protein fraction profile after competitive racing activity in Thoroughbred horses.

In this preliminary investigation, various hematologic variables potentially influential in determining the degree of blood viscosity were evaluated in 10 Thoroughbred horses subjected to competitive acute running exercise. Following completion of sprints over a distance of 1.25 miles, mean percent (+/- SD) increases in PCV (38.3 +/- 12.9%), RBC (47.8 +/- 15.3%), and rouleaux index (232.7 +/- 176.8%) were recognized. Simultaneous increases in total plasma protein (28.3 +/- 5.31%), serum albumin (26.7 +/- 6.80%), alpha 1-globulin (60.0 +/- 49.0%), alpha 2-globulin (25.5 +/- 27.9%), beta 1-globulin (46.7 +/- 21.1%), beta 2-globulin (35.0 +/- 50.6%), gamma 1- and 2-globulins (38.7 +/- 29.6%), and plasma fibrinogen (12.5 +/- 10.4%) concentrations increased simultaneously. Horses also had consistent decreases in albumin:globulin ratio (-10.0 +/- 7.43%). Alterations in these hematologic values after acute running exercise in Thoroughbred horses accompanied increases in serum (69.3 +/- 39.7%), plasma (39.7 +/- 11.9%), and blood (134.7 +/- 55.3%) viscosity.

Absorption of bovine colostral immunoglobulins G and M in newborn foals.

The uptake of colostral IgG and IgM, their serum half-lives, and the rates of endogenous synthesis of IgG and IgM were evaluated in 6 newborn foals fed bovine colostrum (principals) and 6 foals allowed to suckle their dams (controls). The principal foals were fed 400 ml of bovine colostrum (IgG, 10,000 mg/dl and IgM, 200 mg/dl) at 2-hour intervals, from 2 to 20 hours after foaling (total dose, 4 L). Serum IgG and IgM concentrations were determined by single radial immunodiffusion from birth to 98 days of age. At foaling, principal foals had no detectable serum equine IgG, but 1 control foal had serum equine IgG of 185 mg/dl. After ingestion of colostrum, there was no significant difference in the maximal serum bovine IgG concentration (range, 1,350 to 3,300 mg/dl) in the principal foals, and maximal serum equine IgG concentration in the control foals (range, 500 to 6,000 mg/dl). The calculated biological bovine and equine IgG half-life in the principal and control groups was 9.4 and 26 days, respectively. Endogenous IgG synthesis was first detected in 1 principal foal at 3 days of age, but was detected first between 28 and 42 days in the other principal foals. Starting on day 56 there was no significant difference in serum equine IgG concentration between groups. At foaling, foals in both groups had low equine IgM concentrations. In the control foals, there was marked individual variation in the increases in equine IgM concentration (range, 5 to 73 mg/dl) after ingestion of colostrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement activity and selected hematologic variables in newborn foals fed bovine colostrum.

Serum complement activity and selected hematologic variables were evaluated in 5 newborn foals fed bovine colostrum (principal group) and 6 foals allowed to nurse their dam (control group). Also, bovine colostrum was evaluated for anti-equine antibodies. Precolostral serum hemolytic and conglutinating complement activities were low and increased similarly in foals of both groups to reach adult values between 1 and 3 weeks after birth. Bovine colostrum strongly agglutinated, but did not hemolyse principal foals' RBC and blood containing all known equine blood group alloantigens. Hemolysis was not detected after administration of bovine colostrum. Physiologic anemia developed in foals of principal and control groups during the first week of life. Erythrocyte osmotic fragility in foals of the principal group prior to and after the ingestion of colostrum remained unchanged. However, at 36 hours after birth, there was a significant decrease in erythrocyte osmotic fragility in foals fed homologous colostrum.

Colostral volume and immunoglobulin G and M determinations in mares.

Colostral volume and IgG and IgM concentrations were determined in 6 multiparous mares at foaling and them every 2 hours from 16 to 20 hours after parturition. Serum IgG and IgM concentrations at foaling also were determined in each mare. The rate of mammary secretion was 292 +/- 26 ml/h (range, 202 to 389 ml/h), and the colostral volume was 5.1 +/- 0.5 L (range, 3.2 to 7.0 L). The colostral IgG and IgM contents were 440 +/- 106 g (range, 199 to 855 g) and 3.1 +/- 0.9 g (range, 0.7 g to 7.1 g), respectively. There was no significant correlation between serum and initial colostral IgG and IgM concentration or between serum and total colostral IgG or IgM values. The colostral IgG and IgM concentrations at foaling correlated well with the total colostral IgG and IgM contents, respectively. The initial 250 ml of colostrum contained 10 +/- 1.4% (range, 6.0 to 13.9%) and 6 +/- 1.0% (range, 2.4 to 8.5%) of the total IgG and IgM contents, respectively, and the initial 500 ml of colostrum contained 20 +/- 2.7% (range 12.0 to 27.1%) and 14 +/- 1.2% (8.2 to 17%) of the total colostral IgG and IgM contents, respectively.

Pharmacokinetics, bioavailability, and in vitro antibacterial activity of rifampin in the horse.

The pharmacokinetics and bioavailability of rifampin were determined after IV (10 mg/kg of body weight) and intragastric (20 mg/kg of body weight) administration to 6 healthy, adult horses. After IV administration, the disposition kinetics of rifampin were best described by a 2-compartment open model. A rapid distribution phase was followed by a slower elimination phase, with a half-life (t1/2[beta]) of 7.27 +/- 1.11 hours. The mean body clearance was 1.49 +/- 0.41 ml/min.kg, and the mean volume of distribution was 932 +/- 292 ml/kg, indicating that rifampin was widely distributed in the body. After intragastric administration of rifampin in aqueous suspension, a brief lag period (0.31 +/- 0.09 hour) was followed by rapid, but incomplete, absorption (t1/2[a] = 0.51 +/- 0.32 hour) and slow elimination (t1/2[d] = 11.50 +/- 1.55 hours). The mean bioavailability (fractional absorption) of the administered dose during the first 24 hours was 53.94 +/- 18.90%, and we estimated that 70.0 +/- 23.6% of the drug would eventually be absorbed. The mean peak plasma rifampin concentration was 13.25 +/- 2.70 micrograms/ml at 2.5 +/- 1.6 hours after dosing. All 6 horses had plasma rifampin concentrations greater than 2 micrograms/ml by 45 minutes after dosing; concentrations greater than 3 micrograms/ml persisted for at least 24 hours. Mean plasma rifampin concentrations at 12 and 24 hours after dosing were 6.86 +/- 1.69 micrograms/ml and 3.83 +/- 0.87 micrograms/ml, respectively. We tested 162 isolates of 16 bacterial species cultured from clinically ill horses for susceptibility to rifampin.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and estimated bioavailability of amoxicillin in mares after intravenous, intramuscular, and oral administration.

The pharmacokinetics and estimated bioavailability of amoxicillin were determined after IV, intragastric, and IM administration to healthy mares. After IV administration of sodium amoxicillin (10 mg/kg of body weight), the disposition of the drug was best described by a 2-compartment open model. A rapid distribution phase was followed by a rapid elimination phase, with a mean +/- SD half-life of 39.4 +/- 3.57 minutes. The mean volume of distribution was 325 +/- 68.2 ml/kg, and the mean body clearance was 5.68 +/- 0.80 ml/min.kg. It was concluded that frequent IV administration of sodium amoxicillin would be required to maintain therapeutic plasma concentrations of amoxicillin, and thus, the use of this dosage form should be limited to the initiation of treatment or to intensive care situations. After intragastric administration of amoxicillin trihydrate (20 mg/kg), 5% cherry-flavored suspension, the drug was rapidly, but incompletely, absorbed and rapidly eliminated (mean half-life of the decline phase of the plasma amoxicillin concentration-time curve, 51 minutes). The mean estimated bioavailability (fractional absorption) of the administered dose was 10.4%, and the mean peak plasma amoxicillin concentration was 2.73 micrograms/ml at 1.5 hours after dosing. In one horse with clinical signs of abdominal discomfort and diarrhea, the absorption of amoxicillin from the gastrointestinal tract was delayed and the fraction absorbed was increased. It was concluded that this oral dosage form could be recommended only for the treatment of infections caused by bacteria that are highly susceptible to amoxicillin, that frequent dosing would be necessary, and that absorption may be inconsistent in horses with gastrointestinal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydramnios causing uterine rupture in a mare.

An 18-year-old mare, 285 days pregnant, was evaluated for apparent abdominal pain of 8 hours' duration. A large volume of sanguinous fluid was obtained on abdominocentesis, and digital vaginal examination revealed a dilated cervix and blood in the uterus. Abdominal palpation per rectum revealed the uterus to be large and distended with fluid. Ultrasonography revealed a dead fetus on the floor of the cranial portion of the abdomen. The mare was euthanatized, and necropsy confirmed that the uterus had ruptured, and that the fetus, within its chorioallantois, was in the abdomen. The amniotic sac contained approximately 96 L of amniotic fluid. Torsion of the amniotic sac separated the fetus from the fluid-filled compartment. Hydramnios was diagnosed on the basis of the excessive amniotic fluid and was believed to be the cause of the uterine rupture.

Plasma, red blood cell, total blood, and extracellular fluid volumes in healthy horse foals during growth.

During the growth interval encompassing age 2 days through 24 weeks, plasma, RBC, total blood, and extracellular fluid (ECF) volumes were determined in 7 healthy, resting foals. Evans blue dye and sodium thiocyanate were used to estimate plasma and ECF volumes, respectively. Absolute plasma volume remained stable from 2 days through 2 weeks of age, then increased progressively through 24 weeks of age. After decreasing between 2 days and 2 weeks of age, absolute RBC and total blood volumes progressively increased. Absolute ECF volume increased progressively from 2 days of age through 24 weeks of age, but plasma, RBC, and total blood volumes decreased relative to body weight increase. During the first 12 weeks of life, ECF volume decreased relative to body weight increase, and then remained stable during the next 12 weeks. There were close correlations between age, as well as body weight, and plasma, RBC, total blood, and ECF volumes. The relationship defined between age and the respective fluid and blood volumes provided a useful tool for evaluation and management of alterations of fluid balance in the foal.

Pharmacokinetics and endometrial tissue concentrations of ticarcillin given to the horse by intravenous and intrauterine routes.

Plasma and endometrial tissue concentrations of ticarcillin were measured in healthy mares. In the first of the 3 separate phases comprising the study, ticarcillin disodium (30 mg/kg) was administered IV. The mean peak concentration in endometrial tissue, 12.9 micrograms/g, was attained at 30 minutes. The plasma half-life of the drug in the 6 mares was 0.83 +/- 0.22 hour. Six grams of the drug was diluted in 250 ml of sodium chloride injection USP (2nd phase) and in 60 ml of sodium chloride injection USP (3rd phase). These dilutions were administered by intrauterine infusion. In phase 2, the mean peak concentrations of the drug in plasma and endometrium were 2.76 micrograms/ml and greater than 150 micrograms/g, respectively, at 60 minutes after it was administered. Endometrial concentrations greater than 150 micrograms of ticarcillin/g persisted through 2 hours after the drug was administered. Mean peak plasma and endometrial concentrations of the drug in phase 3 were 2.78 micrograms/ml and greater than 150 micrograms/g at 45 and 30 minutes after administration was done, respectively. At 1 hour after the drug was administered, endometrial concentrations of ticarcillin were significantly higher (P less than 0.01) after the drug was infused intrauterinely in the 250-ml volume than those after the 60-ml volume was infused. It was concluded that the volume of fluid in which the drug was infused into the uterus markedly influenced the duration of concentrations greater than 20 micrograms/g in endometrial tissue.