Pilot evaluation of a novel unilateral onychectomy model and efficacy of an extended release buprenorphine product.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs), transdermal fentanyl patches, and transmucosal buprenorphine are probably the most commonly used options for providing post-operative analgesia in the early at-home period. However, these require daily administration or are associated with abuse concerns. One of the significant unmet needs in veterinary surgery and pain management is for longer acting opioids for cats to effectively bridge the gap between the in-hospital and at-home recovery periods. A proof of concept study of an extended release formulation of buprenorphine HCL (ER-Bup) was conducted using objective kinetic measures and a unilateral onychectomy model. Using a blinded, randomized, two period crossover design, four cats were allocated to control (saline) or ER-Bup (0.6 mg/kg, subcutaneously [SC]) treatment groups. All animals underwent a unilateral forelimb onychectomy per period with a washout/recovery period in between. Observational pain scores and kinetic data (using a pressure sensitive walkway [PSW]) were collected prior to (baseline) and at intervals for 72 h following surgery. Symmetry indices were derived for kinetic variables (peak vertical force [PVF]; vertical impulse [VI]) of each forelimb for landing following a jump and for walking. A rescue analgesic protocol was in place. Effect of surgery and treatment were evaluated using a mixed model statistical approach. RESULTS: No cats required rescue analgesics based on subjective pain score. ER-Bup had a positive influence on subjective pain scores during the 72 h postsurgery (p = 0.0473). PVF and VI of the operated limb were significantly decreased for both landing (p < 0.0001 and p < 0.0001) and walking (p < 0.0001 and p < 0.0001 respectively) compared to control. ER-Bup resulted in significantly decreased asymmetry in limb use during landing (PVF, p < 0.0001; VI, p < 0.0001) and walking (PVF, p = 0.0002, VI, p < 0.0001). The novel use of data collected following a jump from an elevated platform appeared to provide all desired information and was easier to collect than walking data. CONCLUSION: This study demonstrates that SC administration of ER-Bup may be an effective analgesic for a 72 h period postoperatively. Furthermore, landing onto a PSW from an elevated perch may be a useful and efficient way to assess analgesics in cats using a unilateral model of limb pain.

Preliminary study on the acaricidal efficacy of spinosad administered orally to dogs infested with the brown dog tick, Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae).

Spinosad is a novel mode of action insecticide and acaricide derived from a family of natural compounds produced from fermentation of the actinomycete, Saccharopolyspora spinosa. Although spinosad has been shown to have rapid knockdown and 1 month of residual efficacy against fleas (Ctenocephalides spp.) following oral administration in dogs, potential activity against ticks infesting dogs has not been determined. To address this possibility, a proof-of-concept laboratory efficacy study was conducted using dogs orally treated with spinosad and experimentally infested with the brown dog tick, Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae). In this randomized block (blocked by gender and pre-treatment tick counts), blinded, parallel-arm study, 12 dogs selected on health and ability to maintain pre-treatment tick populations were allocated equally among three groups: placebo-treated negative control, and spinosad in gelatin capsules at 50 and 100mg/kg administered per os. All treatments were administered once on Day 0. On days -6, -1, 7, 14, 21 and 28, each dog was infested with 50 unfed adult R. sanguineus, approximately 50% male and 50% female, obtained from the investigator's established tick colony. Tick comb counts were performed approximately 48 h post-infestation by study personnel who were blinded to treatments. Compared to geometric mean live tick counts in the control group, tick counts in the 50 and 100mg/kg spinosad doses were significantly (P<0.05) reduced by 94.8 and 97.2%, respectively, within 24h of treatment. Compared to geometric mean live tick counts in the control group at Days 9, 16, 23 and 30 after treatment, the 50mg/kg spinosad treatment group demonstrated 67.8, 49.1, 52.1 and 5.0% reductions, while the 100mg/kg spinosad treatment group demonstrated 88.6, 70.6, 61.9 and 71.3% reductions, respectively. This pilot efficacy study demonstrated that a single oral treatment with technical spinosad in gelatin capsules, at 50 and 100mg/kg, provides high efficacy against existing R. sanguineus infestations within 24h of dosing, and suggests that there is some post-treatment residual tick control in dogs for up to 1 month.

Preliminary studies on the effectiveness of the novel pulicide, spinosad, for the treatment and control of fleas on dogs.

Spinosad is a novel mode-of-action insecticide produced from a family of natural products derived from fermentation of the actinomycete, Saccharopolyspora spinosa. Separate studies were undertaken to determine the minimum effective dose of spinosad given orally for the treatment of experimentally induced flea infestations (Ctenocephalides felis) on dogs, and to assess any potential impacts of feeding canned or dry food at the time of dosing. Both were randomized block (blocked by gender and pre-treatment flea counts), blinded parallel-arm studies, with dogs selected on health and ability to maintain pre-treatment flea populations. For dose selection, 48 dogs were allocated among six groups (8dogs/group; 4 males, 4 females): placebo-treated negative control, spinosad in gelatin capsules at 15, 20, 30 and 40mg/kg administered per os; and topical imidacloprid (10mg/kg) as a positive control. Placebo and spinosad treatments were administered on Days 0, 30 and 60, imidacloprid only on Day 0. In a second study to assess the impact of food type at the time of dosing, three groups were formed: placebo-treated control (8 dogs; 4 males, 4 females), spinosad (30mg/kg) administered with canned food (8 male dogs, 8 females); and spinosad (30mg/kg) with dry food (8 males, 8 females). Treatments were administered on Days 0 and 30. To assess post-treatment persistent efficacy, flea infestations were repeated at regular post-treatment intervals, beginning on Day 5 through Day 89 in the dose selection study and Day 58 in the impact of food type and dosing study. Flea counts were performed 48h post-infestation by study personnel who were blinded to treatments. In the dose selection study, compared to geometric mean live flea counts in the control group, each spinosad dose was highly effective (99.8-100%) at 7, 14 and 21 days after treatment. Only the 30 and 40mg/kg doses maintained high efficacy (97.2-100%) until 30 days after treatment, with no difference between the two. Imidacloprid was highly effective at Day 30, with significant difference only from the 15mg/kg spinosad group. Because there was no significant difference between the higher spinosad rates, 30mg/kg was selected as the optimal minimum effective dose. In the second study, spinosad was highly effective at all post-treatment flea counts (98-100%). Taken together, these studies demonstrate that repeated monthly oral treatments with spinosad at 30mg/kg provide sustained control of C. felis on dogs. There were no treatment-related adverse events in either study, indicating that spinosad has potential to be used monthly as a safe and effective flea adulticide, providing sustained activity that matches that of currently used topical products.