Detection times of clodronic acid in horses with orthopedic disease.

Clodronic acid is designated as a controlled medication for competition horses by the International Federation for Equestrian Sports and, according to the International Federation of Horseracing Authorities, clodronic acid is not to be administered to racehorses younger than 3.5 years or within 30 days prior to a race. In this study, 35 horses involved in competition were treated with a single dose of 1.53 mg clodronic acid/kg bodyweight intramuscularly. Plasma samples were obtained before treatment and 10, 20, 30, and 40 days post-administration. Clodronic acid concentrations were measured using a validated method, and the data were fitted using a nonlinear mixed effects model. The estimated depletion half-life of clodronic acid was 10.6 days (inter-individual variability: 17.9%). Age, body weight, sex, disease severity, dose, training days, training, and competition did not significantly impact the depletion half-life. The percentage of horses predicted via simulation to have clodronic acid concentrations below the assay's limit of quantification of 1.0 ng/mL was 93.9% at day 30 and 99.4% at Day 40. This study provides rationale to the equestrian federations and horse racing authorities to reliably establish a detection time for clodronic acid, assisting equine veterinarians in recommending a competition withdrawal time for the horses under their care.

Enflicoxib for canine osteoarthritis: A randomized, blind, multicentre, non-inferiority clinical trial compared to mavacoxib.

BACKGROUND: This prospective, multisite, blinded, randomized, non-inferiority clinical study aimed to confirm the efficacy and safety of enflicoxib in the treatment of pain and inflammation associated with canine osteoarthritis. A total of 180 dogs were randomized to receive enflicoxib (n = 78), mavacoxib (n = 80) or placebo (n = 22). Dogs underwent veterinary assessments from day 0 to day 42 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). The primary efficacy endpoint was the overall CSS from day 0 to day 42. RESULTS: The overall CSS expressed as area under the curve demonstrated non-inferiority of enflicoxib compared to mavacoxib, and both showed superiority over placebo. At the end of the study, average CSS, and the percentage of CSS responders for enflicoxib (3.64 and 74%) and mavacoxib (4.49 and 68%), was superior to placebo (7.15 and 29%). A faster onset of action was observed for enflicoxib as superiority over placebo was evidenced from the first efficacy assessment (day 7) onwards for both parameters, whereas mavacoxib was only significantly different from day 14 onwards. According to the owner assessment, the percentage of CBPI responders was 90%, 79%, and 43% for dogs treated with enflicoxib, mavacoxib and placebo, respectively, and superiority over placebo was demonstrated for both active treatments. In all secondary parameters, non-inferiority of enflicoxib versus mavacoxib was confirmed. The dog's quality of life improved in all groups, but only enflicoxib showed superiority versus placebo. When assessing severely affected dogs only, results were similar, thus confirming the efficacy of enflicoxib in all stages of canine OA. There were no differences between groups in the frequency of adverse events, which were most frequently mild affecting the gastrointestinal tract and recovered without treatment. CONCLUSIONS: Enflicoxib is efficacious and safe for the treatment of pain and inflammation in any stage of canine osteoarthritis with a faster onset of action compared to mavacoxib.

Efficacy and safety of enflicoxib for treatment of canine osteoarthritis: A 6-week randomised, controlled, blind, multicentre clinical trial.

BACKGROUND: Enflicoxib is a new COX-2 selective NSAID intended for the treatment of pain and inflammation associated with canine osteoarthritis. METHODS: A prospective, multisite, blinded, randomised, controlled, parallel-group field study was performed to determine the efficacy and safety of enflicoxib in canine osteoarthritis. A total of 242 dogs were randomised to receive enflicoxib at 4 or 2 mg/kg, mavacoxib at 2 mg/kg or placebo, orally. Enflicoxib and placebo were administered once weekly from day 0 to day 35. Mavacoxib was administered on D0 and day 14. Veterinarians assessed efficacy with a numerical rating scale and owners used the Canine Brief Pain Inventory. RESULTS: After 6 weeks, enflicoxib at 4 mg/kg showed the highest percentage of responders as assessed by the veterinarians (68%) and the owners (84%), followed by mavacoxib (62and 83%, respectively), and enflicoxib at 2 mg/kg (57 and 80%, respectively). All treatments reached statistical significance versus placebo, which obtained success rates of 37% and 53%, respectively. No differences in the incidence of adverse reactions were detected among the different groups. CONCLUSIONS: Enflicoxib administered weekly for 6 weeks, at 4 mg/kg PO with an initial loading dose of 8 mg/kg, is efficacious and safe for the treatment of canine osteoarthritis.

Anamnestic responses in pigs to the Taenia solium TSOL18 vaccine and implications for control strategies.

Specific antibody responses were assessed in pigs immunized with the Taenia solium vaccine TSOL18. Anti-TSOL18 responses were compared 2 weeks after secondary immunization, where the interval between primary and secondary immunization was 4, 8, 12, 16 or 20 weeks. All animals responded to the vaccine and there was no diminution in antibody responses in animals receiving their second injection after an interval up to 20 weeks. Pigs receiving vaccinations at an interval of 12 weeks developed significantly increased antibody responses compared with animals receiving immunizations 4 weeks apart (P = 0.046). The ability to deliver TSOL18 vaccination effectively where the revaccination schedule can be delayed for up to 12-16 weeks in pigs increases the options available for designing T. solium control interventions that incorporate TSOL18 vaccination.

Persistent efficacy of a long acting injectable formulation of moxidectin against natural infestations of the sheep nasal bot (Oestrus ovis) in Spain.

Cydectin(®) 2% LA Solution for Injection for Sheep (Pfizer Animal Health) is a long-acting (LA) formulation of moxidectin for the treatment and prevention of mixed infections of gastro-intestinal nematodes, respiratory nematodes and certain arthropod parasites in sheep. To evaluate the duration of persistent efficacy against nasal bots (Oestrus ovis), a natural exposure study was conducted in Spain during the summer of 2011. One hundred and twenty nasal bot-free, Rasa Aragonesa sheep were randomly allocated to eight groups of 15 animals each. On Day 0, four groups were treated at the recommended dose rate of 1 mg moxidectin/kg bodyweight. Four groups remained untreated as negative controls. All animals were held in nasal bot-proof housing except for exposure to natural challenge when one group of treated sheep and one of group of control animals were transferred to a local pasture at either 0-20, 20-40, 40-60, or 60-80 days after treatment. Following challenge, sheep were scored for clinical signs of bot infestation, necropsied and the heads sectioned for larval recovery. Nasal bot larvae were retrieved from 7 to 11 control sheep following each exposure period indicating that adult bots were active throughout the study. In the first challenge up to 20 days after treatment, when sheep were slaughtered immediately after exposure, the majority of larvae were first instar (L1) and only 3 of the 15 control sheep were infested with second instars (L2). There was 100% efficacy against L2 and 38.1% reduction in the number of live L1 in the treated sheep but mean counts were not significantly different between treatment and control groups (P ≥ 0.05). For the subsequent exposure periods 20-80 days after treatment (necropsies 7-9 days after challenge), 6-10 sheep were infested with L1 and 9-11 control sheep were infested with L2 and third instars (L3). There was negligible efficacy against L1, but treatment with moxidectin resulted in 100% control of L2 and L3. These results are consistent with the biology of nasal bots and control with a systemic agent, as the slower growing L1 have limited feeding and are therefore less susceptible to systemic parasiticides. The study demonstrated that the persistent efficacy of this long-acting injectable formulation of moxidectin protects against the development of active O. ovis infestations for at least 80 days after treatment.

Inactivated PCV2 one shot vaccine applied in 3-week-old piglets: improvement of production parameters and interaction with maternally derived immunity.

The present study describes the effects of a commercially available vaccine against Porcine circovirus type 2 (PCV2) on clinical, pathological and virological outcomes of 3-week-old piglets from two farms with a clinical history of postweaning multisystemic wasting syndrome (PMWS). The study was a controlled, double-blinded, parallel group (1:1) and randomized trial (with a negative control) involving a total of 1239 animals. The study period comprised from weaning age (time of vaccination or PBS inoculation) until the first shipment of pigs to the slaughterhouse. The vaccine product was able to reduce clinical signs, PCV2 viral load in sera and faeces, and overall mortality in nurseries and fattening units. Moreover, average daily gain was significantly higher in vaccinated versus non-vaccinated piglets during the trial period. On the other hand, it was shown that maternally derived antibodies interfered with the development of an active humoral immune response after PCV2 vaccination.

Pharmacokinetic and pharmacodynamic profiles of danofloxacin administered by two dosing regimens in calves infected with Mannheimia (Pasteurella) haemolytica.

The pharmacokinetics and pharmacodynamics of danofloxacin in calves with induced Mannheimia (Pasteurella) haemolytica pneumonia were evaluated. Calves received either saline as an intravenous (IV) bolus or danofloxacin (0.738 mg/kg of body weight) administered as either a single IV bolus or a 36-h continuous IV infusion. Blood samples and bronchial secretions were collected before and at predetermined times over 48 h following the start of treatment. Calves were assessed clinically throughout, and lung consolidation was assessed at necropsy. Bronchial secretions and lung tissue were cultured for M. haemolytica. Bolus administration of danofloxacin produced a high maximum drug concentration-to-MIC ratio (C(max):MIC) of 14.5 and a time period of 9.1 h when plasma danofloxacin concentrations exceeded the MIC (T>MIC). Following danofloxacin infusion, the C(max):MIC was low (2.3), with a long T>MIC (33.3 h). The area under the curve-to-MIC ratios were 43.3 and 49.1 for the bolus and infusion administrations, respectively. The single bolus of danofloxacin was more effective than the same dose administered by continuous infusion, as indicated by a significantly lower (P < 0.05) number of animals with M. haemolytica in bronchial secretions after treatment and lower rectal temperatures in the 24 h after the start of treatment. Thus, danofloxacin exhibited concentration-dependent antimicrobial activity in cattle with respiratory disease caused by M. haemolytica.