A Comparison of Buprenorphine, Sustained release Buprenorphine, and High concentration Buprenorphine in Male New Zealand White Rabbits

Abstract

Pain management in rabbits can be difficult because they are adept at hiding pain and can be stressed by handling and restraint for injection. The use of opioid analgesics with prolonged durations of activity could alleviate pain, but associated adverse effects including gastrointestinal ileus, inappetence, and tissue reactions have been reported. In this study, we compared gross tissue reactions at the site of injection, food consumption, and fecal production after single injections of buprenorphine HCl (Bup; n = 7), sustained-release buprenorphine (BupSR; n = 8), and high-concentration buprenorphine(BupHC; n = 7) during the first 3 d after minor survival surgery. We also measured plasma concentrations of the parent drug,buprenorphine, and 3 metabolites (buprenorphine-3-glucuronide (B3G), norbuprenorphine-3β-glucuronide (N3G), and norbuprenorphine (NB)). Plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for 4 h for Bup and 42 h for BupHC. For BupSR, plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for approximately 77 h, starting 15 h after administration. For all 3 formulations, N3G was the mostprominent metabolite in the blood. No injection site reactions were visible grossly in any rabbit. Relative to baseline measuresand compared with controls (n = 8), food consumption was suppressed on days 1 through 3 in rabbits that received BupSR and on days 2 through 3 in those given BupHC. Feces production on day 3 was reduced to a greater extent in BupSR rabbits than control animals. Two rabbits in the BupHC group exhibited neurologic signs after drug administration. These adverse effects should be considered when choosing a long-lasting buprenorphine formulation to manage pain in rabbits.

Evaluation and comparison of pharmacokinetic profiles and safety of two extended-release buprenorphine formulations in common marmosets (Callithrix jacchus)

“…However, the use of Simbadol in marmosets as a long-lasting analgesic opioid is less practical because the drug is too concentrated to allow accurate dosing in this small primate species (e.g., 300–450 g) 4 and cannot be diluted. Additionally, Simbadol has been associated with seizures in rabbits 9 , suggesting some species may experience severe adverse events. Zorbium (Elanco) is a recently FDA-approved long-acting transdermal buprenorphine formulation to control postoperative pain in cats for 4 days.…”

“…Buprenorphine, a DEA Schedule III narcotic and partial μ-agonist, δ- and κ-antagonist, and nociceptin receptor agonist 9 – 11 , is the most commonly used opioid analgesic in NHPs, including common marmosets 4 , 12 – 16 . Immediate-release buprenorphine (Bup HCl) dose recommendations for marmosets range from 0.005 to 0.02 mg/kg, either alone for mild to moderate pain, or in multimodal analgesic plans for moderate-to-severe pain 4 , 12 , 14 , 17 , 18 .…”