Discovery and development of veterinary pharmaceuticals in telemetered animals

Abstract

The NMDA antagonist Perzinfotel was tested for anaesthetic sparing properties in telemetered dogs and cats when used in a pre-anaesthetic protocol. In dogs, IV, SQ and IM administration of perzinfotel (10-30 mg/kg) decreased the mean isoflurane MAC values by 32 – 44%. The greatest MAC reduction (59%) was observed with a combination of 20 mg/kg perzinfotel and 0.2 mg/kg butorphanol. Thus, all doses of perzinfotel resulted in a significant reduction of MAC. A dose of 30 mg/kg resulted in significantly higher HR and DAP. Administration of perzinfotel as a pre-anesthetic treatment prior to isoflurane anesthesia improves anesthetic safety by reducing inhalant anesthetic requirements. In cats, IV, IM and SQ administration of perzinfotel (2.5 – 15 mg/kg) significantly decreased mean isoflurane MAC by 43.3 – 68.0%. HR tended to be lower (not significant) and blood pressure was higher compared to placebo. Perzinfotel decreased isoflurane MAC and increased BIS and blood pressure values in anesthetized cats. The administration of perzinfotel as pre-anesthetic medication prior to isoflurane anesthesia should improve anesthetic safety by reducing inhalant anesthetic requirements and improving cardiovascular function during anesthesia. To compare implanted telemetry (DSI) with semi-implanted telemetry (VAP) and a tail cuff, cats were implanted with telemeters and a VAP device. At 4 different time points and under normo- and hypertension, blood pressure was measured with the implanted devices and with NIBP. When comparing VAP and NIPB with DSI, VAP had a correlation coefficient (R2) between 0.8487 and 0.9972 while NIPB had a R2 between 0.7478 and 0.9689. The analgesic properties of perzinfotel, PLA-695 and Carprofen were compared in an induced synovitis pain model in dogs. Compared to baseline values, peak vertical force (PVF) and vertical impulse (VI) for both the negative control and perzinfotel groups had significantly lower forces at 2 and 4 hours. No differences from baseline values for PVF and VI were seen in the PLA-695 or carprofen groups at any measurement time points. Between group comparisons found significantly higher PVF and VI values in the carprofen group vs. the no treatment and perzinfotel groups at 2 and 4 hours. The PLA-695 group had higher impulse values vs. no treatment at 2 hours. The last study investigated the effects on cardiovascular parameters, if any, of a commercially available combination of metaflumizone and amitraz administered to healthy, telemetered beagles that were subsequently sedated with dexmedetomidine. Dogs were sedated first without any pre-treatment and then after pre-treatment with metaflumizone and amitraz. Baseline values of all parameters were within normal limits for all dogs before the first anesthetic event. At 10 and 20 minutes after onset of sedation, oxygen saturation as measured by pulse oxymetry was significantly higher for dogs that were pre-treated with metaflumizone and amitraz. At all times after induction of sedation, blood pressure, heart rate and baseline body temperature for dogs pre-treated with metaflumizone and amitraz were not statistically different from when they were not pre-treated. In conclusion, prior treatment with metaflumizone and amitraz did not influence the hemodynamic response to dexmedetomidine in telemetered dogs.