Evaluation of a human slow-release buprenorphine formulation in rats – tactile sensitivity and plasma concentration

Abstract Background Opioids are considered ideal for managing moderate to severe post-operative pain in laboratory rodents, with buprenorphine being one of the most commonly used analgesics in rats. A long-acting buprenorphine formulation would be highly beneficial to avoid frequent dosing of postoperative animals; however, buprenorphine depot formulations developed for animal use are not available in Europe. The purpose of the present study was therefore to evaluate the effects in rats of a long-acting subcutaneous depot injection with buprenorphine developed for humans (Buvidal). Results Buvidal was evaluated in male Sprague Dawley rats alongside conventional short-acting buprenorphine (Temgesic) delivered subcutaneously and orally, a non-opioid analgesic (carprofen), and controls (saline). All three buprenorphine formulations resulted in significantly reduced mechanical sensitivity when assessed in pain-free, naïve rats using the von Frey pressure test at early time points (3–6 h), whereas carprofen and saline had no effect on tactile sensitivity. In a hypersensitivity model of cephalic allodynia, the hypoalgesic effect of Buvidal lasted beyond 24 h. Plasma concentrations support prolonged drug exposure following administration of the long-acting formulation, and levels exceeding 1 ng/mL were observed during periods of reduced tactile sensitivity. No significant effect on locomotor activity was found in an open field test following buprenorphine administration. Transient pica-like chewing behaviour and reduced alertness were observed in some buprenorphine-treated animals during the first hours after drug administration. Conclusions The human slow-release buprenorphine formulation Buvidal produced sustained systemic exposure and prolonged hypoalgesic effects in male rats, as demonstrated in the cephalic hypersensitivity model, consistent with depot release kinetics. These results show that Buvidal is pharmacologically active in rats and may represent a potential approach for achieving sustained buprenorphine effects in experimental studies requiring prolonged opioid analgesia where rodent-specific formulations are unavailable, although further evaluation of safety, dosing, and generalizability is required.