Pharmacokinetics of Extended-release Buprenorphine (Ethiqa) in Female Yorkshire Swine (Sus scrofa domestica)

Abstract

Despite the use of swine as a large animal translational surgical model, precise dosing regimens for commonly used analgesics such as buprenorphine, are currently lacking in this species. A newly available extended-release formulation of buprenorphine (XRB, Ethiqa) is FDA-indexed and approved for use in mice and rats; however, no studies have examined the efficacy and pharmacokinetic parameters of XRB in swine. The goal of this study was to determine the pharmacokinetics of the newly available XRB in swine. We hypothesized that after a single subcutaneous administration of XRB in adult swine, buprenorphine plasma concentrations would be at or above the therapeutic threshold of 0.1 ng/mL and that local injection side effects would be minimal. XRB was administered once, subcutaneously to two separate cohorts of adult female Yorkshire swine at low and high doses (0.2 and 0.4 mg/kg, respectively; n = 3 and 2). Blood was collected from an indwelling jugular catheter prior to and after XRB administration (13 total time points). Individual animal data indicated all animals reached therapeutic buprenorphine plasma concentrations by 8 h post administration. Average plasma buprenorphine levels for both the low- and high-dose cohorts reached therapeutic concentrations starting at 1.5 h after XRB administration and were maintained above therapeutic concentrations throughout the 96-h study period. In the low-dose cohort, the average half-life was 212.6 {+/-} 107.1 h, whereas the half-lives in the high-dose cohort was 63.8 and 48.9 h. As expected, histology of XRB subcutaneous sites revealed mild injection site reactions characterized by granulomatous inflammation with intralesional cholesterol cleft formation. These results support our hypothesis and indicate that all animals maintained therapeutic plasma buprenorphine levels beginning at 8 h and maintaining past 96 h. Thus, XRB at either dose provide therapeutic levels of plasma buprenorphine and therefore its use should be further explored in swine.