Abstract
Buprenorphine is a commonly used analgesic in laboratory rodents for procedures of moderate to severe pain. We evaluated the pharmacokinetic properties of an immediate-release formulation of buprenorphine (Bup-IR) and an extended-release formulation (Bup-ER) in both sexes of 4 different strains of mice (C57BL/6, CD-1, BALB/c, and CB17 SCID) commonly used for dermatology and oncology research at our institution. Skin at the injection site was evaluated for 7 days postinoculation and scored for reactions and then collected for histopathologic analyses. Body weights were evaluated at 1 and 4 days postinoculation. We hypothesized that the administration of Bup-ER would provide a longer duration of blood drug concentration (>1 ng/mL; minimum analgesia threshold) compared with single-dose Bup-IR. We analyzed the standard dose for Bup-IR (0.3 mg/kg) and for Bup-ER (1 mg/kg), along with saline vehicle with blood collected at 1, 4, 24, 48, 72, and 96 hours following administration of Bup-ER and 0.25, 0.5, 1, 2, 3, 6, 9, 12, and 24 hours following administration of Bup-IR using MS. Bup-ER and Bup-IR levels were consistent among sexes of a given strain but varied between strains. Skin reactions, body weight loss, and histopathologic changes were greater in the Bup-ER-treated mice with some sex and strain differences. Due to changes found on histopathology of the skin sections taken from the injection site for Bup-ER-inoculated mice, a separate study to determine cytokine release following Bup-ER injection was performed and revealed only minor changes in a few cytokines. In conclusion, Bup-ER provided longer duration analgesia (>1 ng/mL) compared with Bup-IR. Based on differences found in the strains of mice evaluated, we recommend performing pharmacokinetic analyses for a given strain to determine the best dosing frequency and dose of buprenorphine (IR or ER) for procedures that require analgesia.