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Effects of route of administration and feeding schedule on pharmacokinetics of robenacoxib in cats
2013
King, Jonathan N. | Jung, Martin | Maurer, Max P. | Schmid, Vincent B. | Seewald, Wolfgang | Lees, Peter
Objective: To establish pharmacokinetics of robenacoxib after administration to cats via the IV, SC, and oral routes. Animals: 24 cats. Procedures: In a crossover design, robenacoxib was administered IV, SC, and orally (experiment 1) and orally (experiment 2) to cats with different feeding regimens. Blood robenacoxib concentrations were assayed, with a lower limit of quantification of 3 ng/mL. Results: In experiment 1, geometric mean pharmacokinetic values after IV administration of robenacoxib were as follows: blood clearance, 0.44 L/kg/h; plasma clearance, 0.29 L/kg/h; elimination half-life, 1.49 hours; and volume of distribution at steady state (determined from estimated plasma concentrations), 0.13 L/kg. Mean bioavailability was 69% and median time to maximum concentration (Cmax) was 1 hour for cats after SC administration of robenacoxib, whereas mean bioavailability was 49% and 10% and median time to Cmax was 1 hour and 30 minutes after oral administration to cats after food withholding and after cats were fed their entire ration, respectively. In experiment 2, geometric mean Cmax was 1,159, 1,201, and 692 ng/mL and area under the curve from 0 to infinity was 1,337, 1,383, and 1,069 ng × h/mL following oral administration to cats after food withholding, cats fed one-third of the daily ration, and cats fed the entire daily ration, respectively. Conclusions and Clinical Relevance: For treatment of acute conditions in cats, it is recommended to administer robenacoxib by IV or SC injection, orally after food withholding, or orally with a small amount of food to obtain optimal bioavailability and Cmax.
Afficher plus [+] Moins [-]Power of treatment success definitions when the Canine Brief Pain Inventory is used to evaluate carprofen treatment for the control of pain and inflammation in dogs with osteoarthritis
2013
Brown, Dorothy Cimino | Bell, Margie | Rhodes, Linda
Objective—To determine the optimal method for use of the Canine Brief Pain Inventory (CBPI) to quantitate responses of dogs with osteoarthritis to treatment with carprofen or placebo. Animals—150 dogs with osteoarthritis. Procedures—Data were analyzed from 2 studies with identical protocols in which owner-completed CBPIs were used. Treatment for each dog was classified as a success or failure by comparing the pain severity score (PSS) and pain interference score (PIS) on day 0 (baseline) with those on day 14. Treatment success or failure was defined on the basis of various combinations of reduction in the 2 scores when inclusion criteria were set as a PSS and PIS ≥ 1, 2, or 3 at baseline. Statistical analyses were performed to select the definition of treatment success that had the greatest statistical power to detect differences between carprofen and placebo treatments. Results—Defining treatment success as a reduction of ≥ 1 in PSS and ≥ 2 in PIS in each dog had consistently robust power. Power was 62.8% in the population that included only dogs with baseline scores ≥ 2 and 64.7% in the population that included only dogs with baseline scores ≥ 3. Conclusions and Clinical Relevance—The CBPI had robust statistical power to evaluate the treatment effect of carprofen in dogs with osteoarthritis when protocol success criteria were predefined as a reduction ≥ 1 in PIS and ≥ 2 in PSS. Results indicated the CBPI can be used as an outcome measure in clinical trials to evaluate new pain treatments when it is desirable to evaluate success in individual dogs rather than overall mean or median scores in a test population.
Afficher plus [+] Moins [-]Efficacy of decontamination and sterilization of a single-use single-incision laparoscopic surgery port
2013
Coisman, James G. | Case, J Brad | Clark, Nadia D. | Wellehan, James F.X. | Ellison, Gary W.
Objective-To determine the efficacy of decontamination and sterilization of a disposable port intended for use during single-incision laparoscopy. Sample-5 material samples obtained from each of 3 laparoscopic surgery ports. Procedures-Ports were assigned to undergo decontamination and ethylene oxide sterilization without bacterial inoculation (negative control port), with bacterial inoculation (Staphylococcus aureus, Escherichia coli, and Mycobacterium fortuitum) and without decontamination and sterilization (positive control port), or with bacterial inoculation followed by decontamination and ethylene oxide sterilization (treated port). Each port underwent testing 5 times; during each time, a sample of the foam portion of each port was obtained and bacteriologic culture testing was performed. Bacteriologic culture scores were determined for each port sample. Results-None of the treated port samples had positive bacteriologic culture results. All 5 positive control port samples had positive bacteriologic culture results. One negative control port sample had positive bacteriologic culture results; a spore-forming Bacillus sp organism was cultured from that port sample, which was thought to be an environmental contaminant. Bacteriologic culture scores for the treated port samples were significantly lower than those for the positive control port samples. Bacteriologic culture scores for the treated port samples were not significantly different from those for negative control port samples. Conclusions and Clinical Relevance-Results of this study indicated standard procedures for decontamination and sterilization of a single-use port intended for use during singleincision laparoscopic surgery were effective for elimination of inoculated bacteria. Reuse of this port may be safe for laparoscopic surgery of animals.
Afficher plus [+] Moins [-]Field study of the comparative efficacy of gamithromycin and tulathromycin for the control of undifferentiated bovine respiratory disease complex in beef feedlot calves at high risk of developing respiratory tract disease
2013
Torres, Siddartha | Thomson, Dan U. | Bello, Nora M. | Nosky, Bruce J. | Reinhardt, Chris D.
Objective-To compare the efficacy of gamithromycin with that of tulathromycin for control of undifferentiated bovine respiratory disease complex (BRDC) in feedlot calves. Animals-2,529 weaned crossbred beef calves. Procedures-At each of 2 feedlots, calves at risk of developing BRDC were administered a single dose of gamithromycin (6.0 mg/kg, SC; n = 1,263) or tulathromycin (2.5 mg/kg, SC; 1,266) metaphylactically. Health (BRDC morbidity, mortality, case-fatality, and retreatment rates) and performance (average daily gain, dry matter intake, and feed-to-gain ratio) outcomes were compared between treatments via classical hypothesis testing. Bioequivalence limits for gamithromycin and tulathromycin were established for outcomes for which no significant difference between treatments was detected. Results-Mean BRDC morbidity rate (31.0%) for calves administered gamithromycin was greater than that (22.9%) for calves administered tulathromycin; otherwise, health and performance did not differ between treatments. Limits for mean differences within which gamithromycin was considered bioequivalent to tulathromycin were +/- 10% for BRDC retreatment rate, +/- 3.5% for BRDC mortality rate, ± 16% for case-fatality rate, +/- 37 kg for final body weight, +/- 0.1 kg/d for average daily gain, +/- 0.3 kg/d for dry matter intake, and +/- 0.7 for feed-to-gain ratio. Conclusions and Clinical Relevance-The efficacy of gamithromycin did not differ from that of tulathromycin for all outcomes except morbidity rate; calves administered gamithromycin had a higher BRDC morbidity rate than did calves administered tulathromycin. On the basis of the bioequivalence limits established for this dataset, gamithromycin was considered equivalent to tulathromycin for the control of BRDC.
Afficher plus [+] Moins [-]Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis)
2013
Evans, Erika E. | Emery, Lee C. | Cox, Sherry K. | Souza, Marcy J.
Objective-To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-6 healthy adult Hispaniolan Amazon parrots. Procedures-A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Results-Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Conclusions and Clinical Relevance-Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.
Afficher plus [+] Moins [-]Evaluation of esophageal high-resolution manometry in awake and sedated dogs
2013
Kempf, Jennifer | Heinrich, Henriette | Reusch, Claudia E. | Kook, Peter H.
Objective-To evaluate the use of high-resolution manometry (HRM) in awake and sedated dogs and to assess potential effects of a standard sedation protocol. Animals-22 Beagles. Procedures-An HRM catheter with 36 pressure sensors was inserted intranasally in each dog. After an adaption period of 5 minutes, each set of measurements included 5 swallows of a liquid and 5 swallows of a solid bolus. Measurements were repeated 30 minutes after IM administration of buprenorphine and acepromazine. Results-HRM was successfully performed in 14 dogs. Data sets of 8 dogs were adequate for analysis. For the upper esophageal sphincter, median values of baseline pressure, residual pressure, relaxation time to nadir, and relaxation duration were determined for awake and sedated dogs for liquid and solid swallows. For the tubular portion of the esophagus, median values of peristaltic contractile integral, bolus transit time, and contractile front velocity were determined for awake and sedated dogs for liquid and solid swallows. For the lower esophageal sphincter, median values of baseline pressure and residual pressure were determined for awake and sedated dogs for liquid and solid swallows. Significant differences (awake vs sedated) were found for the upper esophageal sphincter residual pressure (liquid swallows), relaxation time to nadir (liquid swallows), bolus transit time (solid swallows), and contractile front velocity (solid swallows). Conclusions and Clinical Relevance-HRM was feasible for evaluation of esophageal function in most awake dogs. Although sedation in uncooperative patients may minimally influence results of some variables, an overall assessment of swallowing should be possible.
Afficher plus [+] Moins [-]The effects of dietary omega fatty acids on pregnancy rate, plasma prostaglandin metabolite levels, serum progesterone levels, and milk fatty-acid profile in beef cows
2013
The objectives were to determine the effects of feeding supplements rich in omega-6 or omega-3 fatty acids (FA) during the late gestation to the early postpartum and breeding periods on reproduction and milk FA profile in beef cows. For each of two years, at the beginning of period 1 (mid-December), 72 beef cows, calving in January or February, were assigned to diets supplemented with roasted flaxseed (Flax) or roasted soybean (Soybean). For each of two years, after 11 wk (end of period 1), 18 cows of 36 in the Flax group were switched to the soybean supplement and 18 cows of 36 in the Soybean group were switched to the flax supplement (start of Period 2). Cows were bred by timed artificial insemination (TAI) in week 5 of period 2. The FA composition of the milk reflected the FA profile of the oilseed supplements. There were no differences in pregnancy rates among the 4 groups. The treatments had no effect on plasma prostaglandin metabolite levels or ratios at 4 to 11 d postpartum. At 5 to 6 d post- TAI, pregnant cows fed Flax in period 1 had lower (P < 0.05) plasma prostaglandin F metabolite (PGFM) levels and PGFM to prostaglandin E metabolite (PGEM) ratio than cows fed Soybean, but there were no significant differences at 19 to 20 d post-TAI. Cows pregnant from TAI and fed Flax in period 2 had higher (P < 0.05) serum progesterone levels at 5 to 6 d post-TAI than cows fed Soybean, but there was no difference at 19 to 20 d post-TAI. The dietary treatments had no effect on pregnancy rates, but there were some effects on plasma PGFM levels, PGFM to PGEM ratios, and serum progesterone levels. The FA supplements influenced the FA composition of milk.
Afficher plus [+] Moins [-]Oxidative stress, superoxide production, and apoptosis of neutrophils in dogs with chronic kidney disease
2013
Silva, Adriana Carolina Rodrigues Almeida | Almeida, Breno Fernando Martins de | Soeiro, Carolina Soares | Ferreira, Wagner Luis | Lima, Valéria Marçal Félix de | Ciarlini, Paulo César
Oxidative stress is a key component in the immunosuppression of chronic kidney disease (CKD), and neutrophil function may be impaired by oxidative stress. To test the hypothesis that in uremic dogs with CKD, oxidative stress is increased and neutrophils become less viable and functional, 18 adult dogs with CKD were compared with 15 healthy adult dogs. Blood count and urinalysis were done, and the serum biochemical profile and plasma lipid peroxidation (measurement of thiobarbituric acid reactive substances) were determined with the use of commercial reagents. Plasma total antioxidant capacity (TAC) was measured with a spectrophotometer and commercial reagents, superoxide production with a hydroethidine probe, and the viability and apoptosis of neutrophils with capillary flow cytometry and the annexin V-PE system. The plasma concentrations of cholesterol (P = 0.0415), creatinine (P < 0.0001), and urea (P < 0.0001) were significantly greater in the uremic dogs than in the control dogs. The hematocrit (P = 0.0004), urine specific gravity (P = 0.015), and plasma lipid peroxidation (P < 0.0001) were significantly lower in the dogs that were in late stages of CKD than in the control group. Compared with those isolated from the control group, neutrophils isolated from the CKD group showed a higher rate of spontaneous (0.10 ± 0.05 versus 0.49 ± 0.09; P = 0.0033; median ± standard error of mean) and camptothecin-induced (18.53 ± 4.06 versus 44.67 ± 4.85; P = 0.0066) apoptosis and lower levels of superoxide production in the presence (1278.8 ± 372.8 versus 75.65 ± 86.6; P = 0.0022) and absence (135.29 ± 51.74 versus 41.29 ± 8.38; P = 0.0138) of phorbol-12-myristate-13-acetate stimulation. Thus, oxidative stress and acceleration of apoptosis occurs in dogs with CKD, the apoptosis diminishing the number of viable neutrophils and neutrophil superoxide production.
Afficher plus [+] Moins [-]Computed tomographic evaluation to determine efficacy of euthanasia of yearling feedlot cattle by use of various firearm-ammunition combinations
2013
Thomson, Daniel U. | Wileman, Benjamin W. | Rezac, Darrel J. | Miesner, Matt D. | Johnson-Neitman, Jennifer L. | Biller, David S.
Objective—To evaluate with CT the efficacy of various combinations of firearms and ammunitions to penetrate and disrupt the brain tissue of cadaveric heads of feedlot steers. Sample—42 fresh cadaveric heads of 12- to 18-month-old Bos taurus steers. Procedures—For each of 7 combinations of firearms and ammunitions (.22-caliber rifle firing a long rifle 30-grain plated lead solid- or hollow-point round, .223-caliber carbine firing a 50-grain ballistic-tip round, 9-mm pistol firing a 124-grain total metal jacket round, .45-caliber automatic Colt pistol [ACP] firing a 230-grain full metal jacket round, and 12-gauge shotgun firing a 2.75-inch 1.25-ounce No. 4 birdshot shell or a 1-ounce rifled slug), 6 cadaveric heads were shot at an identical distance (3 m), angle, and anatomic location. Heads were scanned with third-generation CT, and images were evaluated to determine extent of penetration, projectile fragmentation, cranial fracture, and likelihood of instantaneous death (≥ 30% destruction of brain tissue or a brainstem lesion). Results—41 of 42 skulls were penetrated by the projectile. Instantaneous death was considered a likely consequence for 83% (25/30) of heads shot with a rifle-fired .22-caliber solid-point round, pistol-fired .45-caliber ACP round, carbine-fired .223-caliber round, and shotgun-fired birdshot and slug. Of the 18 heads shot with pistol-fired 9-mm and .45-caliber ACP rounds and rifle-fired .22-caliber hollow-point rounds, only 6 had brainstem lesions. Conclusions and Clinical Relevance—Results suggested that gunshots delivered by all firearm-ammunition combinations except rifle-fired .22-caliber hollow-point rounds and pistol-fired 9-mm rounds were viable options for euthanasia of feedlot cattle.
Afficher plus [+] Moins [-]Precision and accuracy of clinical illness scores, compared with pulmonary consolidation scores, in Holstein calves with experimentally induced Mycoplasma bovis pneumonia
2013
Amrine, David E. | White, Brad J. | Larson, Robert | Anderson, David E. | Mosier, Derek A. | Cernicchiaro, Natalia
Objective: To determine the precision of a clinical illness score (CIS) system for identification of clinical signs in calves with experimentally induced Mycoplasma bovis pneumonia and to evaluate the accuracy of CISs in relation to pulmonary consolidation scores assigned at necropsy. Animals: 178 Holstein bull calves that were 52 to 91 days of age at the time of pneumonia induction. Procedures: 5 trials involved calves challenged with M bovis and scheduled for euthanasia and necropsy 12 to 24 days afterward. Nine veterinarian observers with various degrees of experience simultaneously assigned CISs to calves within 48 hours before necropsy. The precision of the CIS system among observers was evaluated via the Cohen κ statistic. The accuracy of each observer's CISs relative to 6 cutoffs (≥ 5%, ≥ 10%, ≥ 15%, ≥ 20%, ≥ 25%, and ≥ 30%) of percentage pulmonary consolidation was determined by comparing prenecropsy CISs with the gross pulmonary consolidation scores assigned at necropsy. Estimates for sensitivity and specificity were calculated relative to the 6 pulmonary consolidation cutoffs. Results: A slight level of agreement was evident among observers (κ range, 0.10 to 0.21 for the individual trials) and overall (κ = 0.16; 95% confidence interval, 0.10 to 0.24). Median sensitivity and specificity changed with pulmonary consolidation score cutoff. Median sensitivity for all observers ranged from 81.7% to 98.9%, and median specificity ranged from 80.8% to 94.9% over all cutoff values. Conclusions and Clinical Relevance: Agreement among observers assigning CISs to calves was low; the accuracy of the CIS system in relation to that of pulmonary consolidation scoring varied with the severity of consolidation considered to represent bovine respiratory disease.
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