Efficacy of Felpreva®, a new spot-on formulation containing tigolaner, emodepside and praziquantel, applied as a single application to cats artificially infested with ear mites (Otodectes cynotis).

The efficacy of Felpreva® (Vetoquinol), a new spot-on application containing the novel acaricide and insecticide tigolaner in combination with emodepside and praziquantel, was evaluated in cats artificially infested with ear mites (Otodectes cynotis). A total of three pivotal dose confirmation studies were conducted, two of them designed as non-interference studies. Cats were artificially infested with O. cynotis mites and randomly allocated into groups of 8 cats based on pre-treatment mite counts. Cats were treated once on Day 0, either with Felpreva® (14.5 â€‹mg/kg tigolaner, 3 â€‹mg/kg emodepside and 12 â€‹mg/kg praziquantel) or with placebo. Studies with a non-interference design included two additional groups of cats, treated with Profender® spot-on solution (Vetoquinol) (3 â€‹mg/kg emodepside and 12 â€‹mg/kg praziquantel) and tigolaner as a mono product (14.5 â€‹mg/kg tigolaner). Efficacy was evaluated on Day 28/Day 30 based on total live mite counts after ear flushing. Efficacy was claimed when: (i) at least six control cats per group were adequately infested with mites; (ii) calculated efficacy was ≥ 90% based on geometric mean mite counts; and (iii) the difference in mite counts between Felpreva®-treated cats and control cats was statistically significant (P â€‹≤ â€‹0.05). In two of the three studies, Felpreva®-treated cats were mite-free (100% efficacy) on Day 28/Day 30 and almost full efficacy (99.6%) was seen in the third study. The difference in mite counts between Felpreva®-treated cats and control cats was significant (P â€‹< â€‹0.0001) in all three studies. All control cats were adequately infested in all three studies. The efficacy of Felpreva® against ear mite (Otodectes cynotis) infection in cats was confirmed.

Disposition of gamithromycin in plasma, pulmonary epithelial lining fluid, bronchoalveolar cells, and lung tissue in cattle.

OBJECTIVE: To determine the disposition of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and lung tissue homogenate in cattle. ANIMALS: 33 healthy Angus calves approximately 7 to 8 months of age. PROCEDURES: Calves were randomly assigned to 1 of 11 groups consisting of 3 calves each, which differed with respect to sample collection times. In 10 groups, 1 dose of gamithromycin (6 mg/kg) was administered SC in the neck of each calf (0 hours). The remaining 3 calves were not treated. Gamithromycin concentrations in plasma, PELF, lung tissue homogenate, and BAL cells (matrix) were measured at various points by means of high-performance liquid chromatography with tandem mass spectrometry. RESULTS: Time to maximum gamithromycin concentration was achieved at 1 hour for plasma, 12 hours for lung tissue, and 24 hours for PELF and BAL cells. Maximum gamithromycin concentration was 27.8 µg/g, 17.8 µg/mL, 4.61 µg/mL, and 0.433 µg/mL in lung tissue, BAL cells, PELF, and plasma, respectively. Terminal half-life was longer in BAL cells (125.0 hours) than in lung tissue (93.0 hours), plasma (62.0 hours), and PELF (50.6 hours). The ratio of matrix to plasma concentrations ranged between 4.7 and 127 for PELF, 16 and 650 for lung tissue, and 3.2 and 2,135 for BAL cells. CONCLUSIONS AND CLINICAL RELEVANCE: Gamithromycin was rapidly absorbed after SC administration. Potentially therapeutic concentrations were achieved in PELF, BAL cells, and lung tissue within 30 minutes after administration and persisted for 7 (PELF) to > 15 (BAL cells and lung tissue) days after administration of a single dose.

Pharmacokinetics of firocoxib after administration of multiple consecutive daily doses to horses.

OBJECTIVE: To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. ANIMALS: 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. PROCEDURES: In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma and urine samples were obtained and analyzed. In a second experiment, 12 horses received IV injections of firocoxib solution once daily for 9 consecutive days, and plasma was obtained and analyzed. RESULTS: Mean +/- SD clearance and steady-state volume of distribution of firocoxib were 40.5 +/- 14.7 mL/h/kg and 2.3 +/- 0.7 L/kg, respectively. Mean half-life was 44.2 +/- 21.6 hours and 36.5 +/- 9.5 hours for IV and oral administration, respectively. The urine concentration- time curve decreased in parallel with the plasma concentration-verus-time curve. Renal clearance (0.26 +/- 0.09 mL/kg/h) was low, compared with total body clearance, which indicated that the main route of elimination was hepatic clearance. CONCLUSIONS AND CLINICAL RELEVANCE: The pharmacokinetics of firocoxib during prolonged use were determined. Use of plasma or urine to ascertain drug concentrations in horses is scientifically valid because the plasma-to-urine ratio was consistent over time and among horses.

Risk of after-hours visits to an in-hospital food animal service by species.

Computer records were accessed documenting in-hospital accessions to the food animal service maintained by the University of Missouri, College of Veterinary Medicine between January 1, 2001 and December 6, 2004. For each species category, the prevalence and relative risk (RR) of after-hours admission were calculated. The prevalence of after-hours visits varied from 0.040 for swine to 0.234 for South American camelidae. Using cattle as a reference level, the relative risk for an after-hours admission was decreased in swine (RR = 0.51) and increased in South American camelidae (RR = 3.04) and sheep or goats (RR = 1.66). The likelihood of an after-hours admission differed significantly among groups.

Effects of phenylbutazone alone or in combination with flunixin meglumine on blood protein concentrations in horses.

OBJECTIVE: To assess effects of treatment with phenylbutazone (PBZ) or a combination of PBZ and flunixin meglumine in horses. ANIMALS: 24 adult horses. PROCEDURE: 13 horses received nonsteroidal antiinflammatory drugs (NSAIDs) in a crossover design. Eleven control horses were exposed to similar environmental conditions. Treated horses received PBZ (2.2 mg/kg, PO, q 12 h, for 5 days) and a combination of PBZ and flunixin meglumine (PBZ, 2.2 mg/kg, PO, q 12 h, for 5 days; flunixin meglumine, 1.1 mg/kg, IV, q 12 h, for 5 days). Serum samples were obtained on day 0 (first day of treatment) and day 5, and total protein, albumin, and globulin were measured. RESULTS: 1 horse was euthanatized with severe hypoproteinemia, hypoalbuminemia, and colitis during the combination treatment. Comparisons revealed no significant difference between control horses and horses treated with PBZ alone. There was a significant difference between control and treated horses when administered a combination of PBZ and flunixin meglumine. Correction for horses with values >2 SDs from the mean revealed a significant difference between control horses and horses administered the combination treatment, between control horses and horses administered PBZ alone, and between horses receiving the combination treatment and PBZ alone. Gastroscopy of 4 horses revealed substantial gastric ulcers when receiving the combination NSAID treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of the study indicates the need for caution when administering a combination NSAID treatment to horses because the detrimental effects may outweigh any potential benefits.

Pharmacokinetics of intravenously administered caffeine in healthy alpacas (Lama pacos) and llamas (Lama glama).

OBJECTIVE: To determine the pharmacokinetic disposition of IV administered caffeine in healthy Lama spp camelids. ANIMALS: 4 adult male alpacas and 4 adult female llamas. PROCEDURES: Caffeine (3 mg/kg) was administered as an IV bolus. Plasma caffeine concentrations were determined by use of high-performance liquid chromatography in 6 animals and by use of liquid chromatography-mass spectrometry in 2 llamas. RESULTS: Median elimination half-life was 11 hours (range, 9.3 to 29.8 hours) in alpacas and 16 hours (range, 5.4 to 17 hours) in llamas. The volume of distribution at steady state was 0.60 L/kg (range, 0.45 to 0.93 L/kg) in alpacas and 0.75 L/kg (range, 0.68 to 1.15 L/kg) in llamas. Total plasma clearance was 44 mL/h/kg (range, 24 to 56 mL/h/kg) in alpacas and 42 mL/h/kg (range, 30 to 109 mL/h/kg) in llamas. CONCLUSIONS AND CLINICAL RELEVANCE: High-performance liquid chromatography and liquid chromatography-mass spectrometry were suitable methods for determination of plasma caffeine concentrations in alpacas and llamas. Plasma caffeine concentration-time curves were best described by a 2-compartment model. Elimination half-lives, plasma clearance, volume of distribution at steady state, and mean residence time were not significantly different between alpacas and llamas. Intravenous administration of caffeine at a dose of 3 mg/kg did not induce clinical signs of excitement.

Observations on macrolide resistance and susceptibility testing performance in field isolates collected from clinical bovine respiratory disease cases.

The objectives of this study were; first, to describe gamithromycin susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolated from cattle diagnosed with bovine respiratory disease (BRD) and previously treated with either gamithromycin for control of BRD (mass medication=MM) or sham-saline injected (control=CON); second, to describe the macrolide resistance genes present in genetically typed M. haemolytica isolates; third, use whole-genome sequencing (WGS) to correlate the phenotypic resistance and genetic determinants for resistance among M. haemolytica isolates. M. haemolytica (n=276), P. multocida (n=253), and H. somni (n=78) were isolated from feedlot cattle diagnosed with BRD. Gamithromycin susceptibility was determined by broth microdilution. Whole-genome sequencing was utilized to determine the presence/absence of macrolide resistance genes and to genetically type M. haemolytica. Generalized linear mixed models were built for analysis. There was not a significant difference between MM and CON groups in regards to the likelihood of culturing a resistant isolate of M. haemolytica or P. multocida. The likelihood of culturing a resistant isolate of M. haemolytica differed significantly by state of origin in this study. A single M. haemolytica genetic subtype was associated with an over whelming majority of the observed resistance. H. somni isolation counts were low and statistical models would not converge. Phenotypic resistance was predicted with high sensitivity and specificity by WGS. Additional studies to elucidate the relationships between phenotypic expression of resistance/genetic determinants for resistance and clinical response to antimicrobials are necessary to inform judicious use of antimicrobials in the context of relieving animal disease and suffering.

Evaluation of a continuous glucose monitoring system for use in veterinary medicine.

BACKGROUND: With the emergence of continuous glucose monitoring systems being used to provide a detailed glucose picture in humans, a commercially available system (CGMS(R), Medtronic Minimed, Northridge, CA) was examined for use in veterinary species. METHODS: Adult, clinically normal horses (n = 7), cats (n = 3), dogs (n = 4), and cows (n = 5) were studied. Cats (n = 4), dogs (n = 5), and one horse with diabetes were included in the study. Several of the normal horses, including the horse with diabetes, and one cow were subjected to an intravenous glucose tolerance test. The CGMS was attached to each animal, and the recorded interstitial glucose concentrations were compared with whole blood glucose concentrations as determined by a point-of-care glucose meter. Events such as insulin administration, feeding, travel, or administration of intravenous glucose were all noted and compared with results from the CGMS. RESULTS: There was a positive correlation between interstitial and whole blood glucose concentrations for all the clinically normal species, those with diabetes mellitus, and those receiving intravenous glucose. Events such as feeding, glucose or insulin administration, and transport to the clinic were noted by the owner or clinician and could be identified on the graph and correlated with time of occurrence. CONCLUSIONS: Our data indicate that the use of the CGMS is valid for use in the species examined. Use of this system alleviated the need for multiple blood samples and the stress associated with obtaining those samples. This system may provide greater monitoring capabilities in patients with diabetes and promote the diagnostic and research potential of serial glucose monitoring in veterinary species.

Comparison of the response of primary human blood monocytes and the U937 human monocytic cell line to two different sizes of alumina ceramic particles.

It is well recognized that wear particles derived from orthopaedic implants have the potential to induce inflammation, which may eventually lead to aseptic loosening of the artificial joint. We hypothesized that alumina ceramic particles of different sizes cause a differential cytokine response by human monocytes. To test this hypothesis a human monocytic cell line (U937) and primary human blood monocytes obtained from healthy volunteers were exposed to ceramic particles within the range known to be generated in vivo. Cellular responses were measured by quantifying the relative gene expression of 12 different cytokines using TAQman Real-Time Polymerase Chain Reaction (RT-PCR). Our results demonstrate that at a particle to cell ratio of 100:1, 0.5 microm ceramic particles consistently provoked higher amounts of Interleukin-1alpha (IL-1alpha), IL-1beta, IL-8, IL-10 and Tumor necrosis factor-alpha (TNF-alpha) steady state mRNA by U937 cells. As expected, the variability of cytokine expression in primary blood monocytes was much higher compared to the cell line however, a similar trend was observed. These results show a differential response to ceramic particle size, which may imply that 0.5 microm particles are less biocompatible. New ceramic implants can be designed to generate a known particle size range in vivo. Implant materials of this type may induce relatively lower levels of production of inflammatory cytokines resulting in a reduced incidence of failure due to aseptic loosening.

Serum immunoglobulin G concentrations in calves fed fresh colostrum or a colostrum supplement.

This study compared serum immunoglobulin G (IgG) concentrations in calves fed colostrum with those of calves fed a colostrum supplement containing spray-dried serum. Twenty-four Holstein calves were randomly assigned to I of 2 treatment groups (fresh colostrum or colostrum supplement). Each calf was fed 4 L of colostrum (n, = 12) or 4 L of colostrum supplement (n2 = 12) via oroesophageal intubation at 3 hours of age. The concentration of the colostrum supplement fed to calves was twice the manufacturer's recommendation. The median and range values for colostral IgG concentration were 6,430 mg/dL and 1,400-17,000 mg/ dL, respectively. Median serum IgG concentrations at 2 days of age differed significantly (P = .001) between calves receiving fresh colostrum (3,350 mg/dL) and the colostrum supplement (643 mg/dL). Eight percent of calves force fed colostrum had serum IgG concentrations < 1,000 mg/dL, whereas 75% of calves force-fed supplement had IgG concentrations below this threshold. The calculated population relative risks for mortality associated with passive transfer for calves force-fed colostrum and calves force-fed colostrum supplement were 1.09 and 1.90, respectively. Force-fed fresh colostrum is superior to the colostrum supplement studied, but the colostrum supplement has similar efficacy to routine colostrum administration practices.

Comparison of refractometers and test endpoints in the measurement of serum protein concentration to assess passive transfer status in calves.

OBJECTIVE: To evaluate 3 refractometers for detection of failure of passive transfer (FPT) of immunity in calves, and assess the effect of refractometric test endpoints on sensitivity, specificity, and proportion of calves classified correctly with regard to passive transfer status. DESIGN: Prospective study. ANIMALS: 90 calves. PROCEDURE: Blood samples were obtained from calves that were < 10 days old. Serum IgG concentration was determined by use of a radial immunodiffusion assay. Accuracy of 3 refractometers in the prediction of serum IgG concentration was determined by use of standard epidemiologic methods and a linear regression model. RESULTS: At a serum protein concentration test endpoint of 5.2 g/dL, sensitivity of each refractometer was 0.89 or 0.93, and specificity ranged from 0.80 to 0.91. For all refractometers, serum protein concentration test endpoints of 5.0 or 5.2 g/dL resulted in sensitivity > 0.80, specificity > 0.80, and proportion of calves classified correctly > 0.85. Serum protein concentrations equivalent to 1,000 mg of IgG/dL of serum were 4.9, 4.8, and 5.1 g/dL for the 3 refractometers. CONCLUSIONS AND CLINICAL RELEVANCE: The refractometers, including a nontemperature-compensating instrument, performed similarly in detection of FPT. Serum protein concentration test endpoints of 5.0 and 5.2 g/dL yielded accurate results in the assessment of adequacy of passive transfer; lower or higher test endpoints misclassified larger numbers of calves.