Objective: To determine the pharmacokinetics of ciprofloxacin in dogs, including oral absorption following administration of generic ciprofloxacin tablets. Animals: 6 healthy Beagles. Procedures: In a crossover study design, ciprofloxacin was administered as a generic tablet (250 mg, PO; mean dose, 23 mg/kg) and solution (10 mg/kg, IV) to 6 dogs. In a separate experiment, 4 of the dogs received ciprofloxacin solution (10 mg/mL) PO via stomach tube (total dose, 250 mg). Blood samples were collected before (time 0) and for 24 hours after each dose. Plasma concentrations were analyzed with high-pressure liquid chromatography. Pharmacokinetic analysis was performed by means of compartmental modeling. Results: When ciprofloxacin was administered as tablets PO, peak plasma concentration was 4.4 μg/mL (coefficient of variation [CV], 55.9%), terminal half-life (t1/2) was 2.6 hours (CV, 10.8%), area under the time-concentration curve was 22.5 μg•h/mL (CV, 62.3%), and systemic absorption was 58.4% (CV, 45.4%). For the dose administered IV, t1/2 was 3.7 hours (CV, 52.3%), clearance was 0.588 L/kg/h (CV, 33.9%), and volume of distribution was 2.39 L/kg (CV, 23.7%). After PO administration as a solution versus IV administration, plasma concentrations were more uniform and consistent among dogs, with absorption of 71% (CV, 7.3%), t1/2 of 3.1 hours (CV, 18.6%), and peak plasma concentration of 4.67 μg/mL (CV, 17.6%). Conclusions and Clinical Relevance: Inconsistent oral absorption of ciprofloxacin in some dogs may be formulation dependent and affected by tablet dissolution in the small intestine. Because of the wide range in oral absorption of tablets, the dose needed to reach the pharmacokinetic-pharmacodynamic target concentration in this study ranged from 12 to 52 mg/kg (CV, 102%), with a mean dose of 25 mg/kg, once daily, for bacteria with a minimum inhibitory concentration ≤ 0.25 μg/mL.

Objective: To develop a better system for classification of herd infection status for paratuberculosis (Johne's disease [JD]) in US cattle herds on the basis of the risk of potential transmission of Mycobacterium avium subsp paratubeculosis. Sample: Simulated data for herd size and within-herd prevalence; sensitivity and specificity for test methods obtained from consensus-based estimates. Procedures: Interrelationships among variables influencing interpretation and classification of herd infection status for JD were evaluated by use of simulated data for various herd sizes, true within-herd prevalences, and sampling and testing methods. The probability of finding ≥ 1 infected animal in herds was estimated for various testing methods and sample sizes by use of hypergeometric random sampling. Results: 2 main components were required for the new herd JD classification system: the probability of detection of infection determined on the basis of test results from a sample of animals and the maximum detected number of animals with positive test results. Tables were constructed of the estimated probability of detection of infection, and the maximum number of cattle with positive test results or fecal pools with positive culture results with 95% confidence for classification of herd JD infection status were plotted. Herd risk for JD was categorized on the basis of 95% confidence that the true within-herd prevalence was ≤ 15%, ≤ 10%, ≤ 5%, or ≤ 2%. Conclusions and Clinical Relevance: Analysis of the findings indicated that a scientifically rigorous and transparent herd classification system for JD in cattle is feasible.

Objective: To evaluate 2 plate designs for pancarpal arthrodesis and their effects on load transfer to the respective bones as well as to develop a computational model with directed input from the biomechanical testing of the 2 constructs. Sample: Both forelimbs from the cadaver of an adult castrated male Golden Retriever. Procedures: CT imaging was performed on the forelimb pair. Each forelimb was subsequently instrumented with a hybrid dynamic compression plate or a castless pancarpal arthrodesis plate. Biomechanical testing was performed. The forelimbs were statically loaded in the elastic range and then cyclically loaded to failure. Finite element (FE) modeling was used to compare the 2 plate designs with respect to bone and implant stress distribution and magnitude when loaded. Results: Cyclic loading to failure elicited failure patterns similar to those observed clinically. The mean ± SD error between computational and experimental strain was < 15% ± 13% at the maximum loads applied during static elastic loading. The highest bone stresses were at the distal extent of the metacarpal bones at the level of the screw holes with both plates; however, the compression plate resulted in slightly greater stresses than did the arthrodesis plate. Both models also revealed an increase in bone stress at the proximal screw position in the radius. The highest plate stress was identified at the level of the radiocarpal bone, and an increased screw stress (junction of screw head with shaft) was identified at both the most proximal and distal ends of the plates. Conclusions and Clinical Relevance: The FE model successfully approximated the biomechanical characteristics of an ex vivo pancarpal plate construct for comparison of the effects of application of different plate designs.

Objective: To assess the agreement and reliability of cardiac measurements obtained with 3 echocardiographic techniques in anesthetized red-tailed hawks (Buteo jamaicensis). Animals: 10 red-tailed hawks. Procedures: Transcoelomic, contrast transcoelomic, and transesophageal echocardiographic evaluations of the hawks were performed, and cineloops of imaging planes were recorded. Three observers performed echocardiographic measurements of cardiac variables 3 times on 3 days. The order in which hawks were assessed and echocardiographic techniques were used was randomized. Results were analyzed with linear mixed modeling, agreement was assessed with intraclass correlation coefficients, and variation was estimated with coefficients of variation. Results: Significant differences were evident among the 3 echocardiographic methods for most measurements, and the agreement among findings was generally low. Interobserver agreement was generally low to medium. Intraobserver agreement was generally medium to high. Overall, better agreement was achieved for the left ventricular measurements and for the transesophageal approach than for other measurements and techniques. Conclusions and Clinical Relevance: Echocardiographic measurements in hawks were not reliable, except when the left ventricle was measured by the same observer. Furthermore, cardiac morphometric measurements may not be clinically important. When measurements are required, one needs to consider that follow-up measurements should be performed by the same echocardiographer and should show at least a 20% difference from initial measurements to be confident that any difference is genuine.

Objective: To develop in genetically engineered mice an alternative screening method for evaluation of P-glycoprotein substrate toxicosis in ivermectin-sensitive Collies. Animals: 14 wild-type C57BL/6J mice (controls) and 21 genetically engineered mice in which the abcb1a and abcb1b genes were disrupted and the mutated canine ABCB1 gene was inserted. Procedures: Mice were allocated to receive 10 mg of ivermectin/kg via SC injection (n = 30) or a vehicle-only formulation of propylene glycol and glycerol formal (5). Each was observed for clinical signs of toxic effects from 0 to 7 hours following drug administration. Results: After ivermectin administration, considerable differences were observed in drug sensitivity between the 2 types of mice. The genetically engineered mice with the mutated canine ABCB1 gene had signs of severe sensitivity to ivermectin, characterized by progressive lethargy, ataxia, and tremors, whereas the wild-type control mice developed no remarkable effects related to the ivermectin. Conclusions and Clinical Relevance: The ivermectin sensitivity modeled in the transgenic mice closely resembled the lethargy, stupor, disorientation, and loss of coordination observed in ivermectin-sensitive Collies with the ABCB1–1Δ mutation. As such, the model has the potential to facilitate toxicity assessments of certain drugs for dogs that are P-glycoprotein substrates, and it may serve to reduce the use of dogs in avermectin derivative safety studies that are part of the new animal drug approval process.

The objective of this study was to evaluate the bactericidal effect of shock waves (SWs) on gram-negative or gram-positive monocultured biofilms grown on an orthopedic implant in vitro. Cortical bone screws were individually cultured with Escherichia coli or Staphylococcus epidermidis to produce a biofilm. In each run of 8 screws, 6 screws were treated with shock waves and then sonicated to disrupt the biofilm. One screw was sonicated only and one was not shock waved or sonicated before sampling for plate count dilutions. Post-treatment serial dilutions and plate counts were done on an aliquot from the vial containing each screw to obtain the number of colony-forming units (CFUs). Shock waves were at a constant energy of 0.15 mJ/mm2. Pulse number and screw orientation were varied. A linear mixed-effects model was used with “treatment” as a fixed effect and “run” as a random effect. Pairwise comparisons of treatments were performed with Tukey-Cramer’s adjustment for P-values. Sonicated plate counts were greater than nonsonicated counts for each run. When all sonicated screws were compared to all nonsonicated screws, the counts were significantly increased (P = 0.0091). For each paired comparison between sonicated and shock wave treatment, the only significant difference was in the S. epidermidis biofilm treated at 2000 pulses in a horizontal position, which increased the post-treatment count (P = 0.0445). No bactericidal effects were seen on monocultured biofilms on cortical bone screws treated with shock waves.

Objective: To optimize the use of CT-guided modeling for the calculation of body surface area (BSA) in domestic rabbits (Oryctolagus cuniculus). Animals: 12 domestic rabbits. Procedures: Adult rabbits (body weight, 1 to > 4 kg) that were client-owned animals undergoing CT for disease diagnosis or deceased laboratory animals donated from other research projects were scanned with a CT scanner. Images were transferred to a radiation therapy planning software program. Image slices were captured as contiguous slices at 100 kVp and 100 mA and processed to 0.1-cm-thick sections. The length of each contoured slice was summed to calculate a final BSA measurement. Nonlinear regression analysis was then used to derive an equation for the calculation of BSA in rabbits. Results: The constant calculated by use of this method was 9.9 (range, 9.59 to 10). The R2 for the goodness of fit was 0.9332. The equation that best described BSA as a function of body weight for domestic rabbits with this method was as follows: BSA = (9.9 × [body weight {in grams}]2/3)/10,000. Conclusions and Clinical Relevance: The BSA calculated via the CT-guided method yielded results similar to those obtained with equations for other similarly sized mammals and verified the use of such equations for rabbits. Additionally, this technique can be used for species that lack equations for the accurate calculation of BSA.

Objective: To establish and validate an objective method of radiographic diagnosis of anatomic changes in laminitic forefeet of donkeys on the basis of data from a comprehensive series of radiographic measurements. Animals: 5 donkeys with and 85 without forelimb laminitis for baseline data determination; a cohort of 44 donkeys with and 18 without forelimb laminitis was used for validation analyses. Procedures: For each donkey, lateromedial radiographic views of 1 weight-bearing forelimb were obtained; images from 11 laminitic and 2 nonlaminitic donkeys were excluded (motion artifact) from baseline data determination. Data from an a priori selection of 19 measurements of anatomic features of laminitic and nonlaminitic donkey feet were analyzed by use of a novel application of multivariate statistical techniques. The resultant diagnostic models were validated in a blinded manner with data from the separate cohort of laminitic and nonlaminitic donkeys. Results: Data were modeled, and robust statistical rules were established for the diagnosis of anatomic changes within laminitic donkey forefeet. Component 1 scores ≤ −3.5 were indicative of extreme anatomic change, and scores from −2.0 to 0.0 denoted modest change. Nonlaminitic donkeys with a score from 0.5 to 1.0 should be considered as at risk for laminitis. Conclusions and Clinical Relevance: Results indicated that the radiographic procedures evaluated can be used for the identification, assessment, and monitoring of anatomic changes associated with laminitis. Screening assessments by use of this method may enable early detection of mild anatomic change and identification of at-risk donkeys.

Objective: To model the plasma tetracycline concentrations in swine (Sus scrofa domestica) treated with medication administered in water and determine the factors that contribute to the most accurate predictions of measured plasma drug concentrations. Sample: Plasma tetracycline concentrations measured in blood samples from 3 populations of swine. Procedures: Data from previous studies provided plasma tetracycline concentrations that were measured in blood samples collected from 1 swine population at 0, 4, 8, 12, 24, 32, 48, 56, 72, 80, 96, and 104 hours and from 2 swine populations at 0, 12, 24, 48, and 72 hours hours during administration of tetracycline hydrochloride dissolved in water. A 1-compartment pharmacostatistical model was used to analyze 5 potential covariate schemes and determine factors most important in predicting the plasma concentrations of tetracycline in swine. Results: 2 models most accurately predicted the tetracycline plasma concentrations in the 3 populations of swine. Factors of importance were body weight or age of pig, ambient temperature, concentration of tetracycline in water, and water use per unit of time. Conclusions and Clinical Relevance: The factors found to be of importance, combined with knowledge of the individual pharmacokinetic and chemical properties of medications currently approved for administration in water, may be useful in more prudent administration of approved medications administered to swine. Factors found to be important in pharmacostatistical models may allow prediction of plasma concentrations of tetracycline or other commonly used medications administered in water. The ability to predict in vivo concentrations of medication in a population of food animals can be combined with bacterial minimum inhibitory concentrations to decrease the risk of developing antimicrobial resistance.