Evaluation of the pharmacodynamics and analgesic efficacy of two buprenorphine formulations in dogs

Abstract

Pain is an unpleasant and distressing experience. While it serves a protective function for a short period, untreated, ongoing pain has significant detrimental effects. Opioids are one of the most important analgesic agents used for pain management in human and veterinary medicine, with the µ opioid agonists being the most effective for moderate to severe pain. Traditional presentations of µ opioid agonists or partial agonists usually require frequent dosing, which can lead to significant stress due to frequent animal restraint, variability in the level of analgesia and can be labor intensive and time consuming for veterinary personal. Buprenorphine has been shown to be effective in the treatment of mild to moderate pain with minimal adverse effects in dogs. Despite having a longer dosing interval than most other mu agonists, buprenorphine still requires hospitalization of clinical patients or intermittent handling of research animals. In recent years, new formulations of buprenorphine have been introduced and have the potential to provide longer duration of action after a single subcutaneous injection. This dissertation presents the pharmacodynamics and analgesic efficacy of two long-lasting buprenorphine formulations in dogs. The first formulation evaluated is a sustained-release buprenorphine (buprenorphine HCL in a proprietary sustained release biodegradable liquid polymer matrix). The pharmacokinetics and selected behavioral, physiologic and antinociceptive effects of two doses of this sustained-release formulation was evaluated in dogs. The antinociceptive effects of this formulation were assessed using a mechanical nociceptive testing threshold device. The second formulation is a high-concentration buprenorphine, which has been approved for use in cats. Selected behavioral, physiologic and antinociceptive effects of two doses of this high-concentration formulation were evaluated in dogs undergoing neutering. The analgesic efficacy of this formulation was evaluated using 3 different pain-scoring systems. Both formulations showed promising results. Sustained-release buprenorphine provided significant increase in mechanical nociceptive thresholds for up to 84 hours after drug administration, while the high-concentration buprenorphine provided effective analgesia with minimal side effects in dogs undergoing neutering for at least 24 hours after drug administration. These findings suggest that both formulations have the potential to be an effective and practical alternative in providing long-lasting analgesia in dogs.