FEB 08, 2017 01:30 PM PST

Safety and pharmacokinetic profiles of different buprenorphine SR doses in a rabbit model

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  • Resident Veterinarian, University of Southern California
      Dr. Zanetti received his PhD in Biomedical Engineering (emphasis in Stem Cell Biology and Tissue Engineering) from Louisiana State University (Pennington Biomedical Research Center) through his work on novel fracture repair strategies using stem cells and biodegradable scaffolding materials. He later assumed a Staff Scientist position at the McGowan Institute of Regenerative Medicine/Heart and Vascular Institute at the University of Pittsburgh Medical Center where he worked with several animal models to develop innovative cellular therapies for vascular repair following arterial injury related to angioplasty and stenting. Currently, he is completing his residency in laboratory animal medicine (clinical emphasis) at the University of Southern California (USC)/City of Hope (COH). Dr. Zanetti is an active reviewer for a number of peer reviewed journals and is also a member of several professional organizations to include the Academy of Surgical Research, the American Association of Laboratory Animal Science, and the American Veterinary Medical Association. In his talk, Dr. Zanetti will give an overview of his ACLAM-funded research findings on the use of varying doses of buprenorphine sustained release in a rabbit orthopedic model.


    DATE: February 8, 2017
    TIME: 1:30pm PT, 4:30pm ET

    In rabbits, buprenorphine instant release (IR) is commonly used to alleviate pain, especially in surgical models. However, maintenance of IR therapeutic levels requires redosing which significantly increases unnecessary animal handling, restraint and non-compliance issues post-operatively. The development of sustained-release (SR) formulations of buprenorphine in rabbits to deliver constant levels of the drug with adequate plasma concentration and satisfactory analgesia would greatly improve standard of care. In here, we hypothesized that single subcutaneous administration of at least one of three SR (Buprenorphine SRTM Lab, ZooPharm) concentrations (SRLow - 0.06 mg/kg, SRMedium - 0.15 mg/kg, SRHigh – 0.3 mg/kg - n = 3 animals per group) is associated with up to 72 hours of pain relief and more predictable behavior and pain-associated parameters than IR (0.05 mg/kg BID) in a bilateral rabbit knee defect model. In addition to body weight, fecal output, grimace and lameness (0-4, where 0 = continuous weight bearing, 1 = single limb lameness, 2 = multiple limb lameness, 3 = toe touch – non-weight bearing, and 4 = completely non-weight bearing) scales were assessed and scored before and for 72 hours after surgery. No skin reaction to any of the tested SR concentrations was observed within the study phase. Post-operative assessment also revealed no significant changes in body weight across groups. Compared to IR and SRHigh, daily fecal output assessment was higher in rabbits treated with SRLow and SRMedium. Single limb lameness and signs of pain (grimace scale) were observed only in rabbits treated with IR (24 hours) and SRLow (24-48 hours). In fact, rabbits treated with SRLow also received meloxicam (0.3 mg/kg PO SID) within the first 48 hours. Compared to IR, SRLow and SRHigh single administration of SRMedium had little effect in the fecal output and behavior of rabbits enrolled in the selected surgical model. Rabbits treated with IR, SRHigh and SRMedium had similar PK values during the first post-operative hours. In SRHigh and SRMedium, the plasma concentration of the drug remained within the 1ng/ml mark for at least 48 hours. In conclusion, rabbits treated with one dose of SRMedium at 0.15 mg/kg had similar post-operative outcome to the observed in animals treated twice a day with the gold standard drug (IR) and significantly less adverse effects when compared to the observed in the SRLow and SRHigh groups. Further investigation is needed to validate this pain management protocol in other rabbits orthopedic models.

    Learning objectives: 

    • Provide an overview of buprenorphine SR pharmacokinetics at different doses and over time.
    • Provide an overview of adverse effects and clinical findings after buprenorphine SR administration.

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