Objective: To determine the pharmacokinetics of extended-release buprenorphine (XRB) in adult swine. We hypothesized that after a single SC administration of XRB in swine, buprenorphine plasma concentrations would be at or above the therapeutic threshold of 0.1 ng/mL and would not result in major injection site reactions.
Methods: Extended-release buprenorphine was administered once SC to 2 cohorts of adult female Yorkshire swine at low (0.2 mg/kg) and high doses (0.4 mg/kg). Blood was collected from an indwelling jugular catheter prior to and after XRB administration for 13 total time points. Buprenorphine plasma concentrations were analyzed by HPLC-MS, and pharmacokinetics were performed using a noncompartmental analysis.
Results: Extended-release buprenorphine was present in plasma at the therapeutic concentration of 0.1 ng/mL or above beginning at 8 hours and maintaining throughout 96 hours for all animals in both cohorts. Average plasma buprenorphine levels for both cohorts reached therapeutic concentrations starting at 1.5 hours and were maintained above therapeutic concentrations throughout 96 hours. The low-dose cohort's (n = 3) average half-life was 212.6 ± 107.1 hours, and the high-dose cohort's (n = 2) was 63.8 and 48.9 hours, respectively. The histology of SC sites revealed mild injection site reactions characterized by granulomatous inflammation with intralesional cholesterol cleft formation.
Conclusions: All animals reached and maintained therapeutic buprenorphine plasma concentrations of 0.1 ng/mL by 8 hours and maintained it to the end of the study at 96 hours.
Clinical Relevance: Extended-release buprenorphine at either dose provides therapeutic levels of plasma buprenorphine, and therefore its use should be further investigated in swine.
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