Pharmacokinetic Profiles of a New Extended-release Buprenorphine Formulation in Cynomolgus Macaques (Macaca fascicularis).

Abstract

The primary objective of this study was to evaluate the pharmacokinetic profile of a new extended-release formulation of buprenorphine (BupBaseER) at a dose that would produce pain management of the desired duration. A secondary objective was to compare the incidence of injection site reactions between the original extended-release formulation (BupHClER) and BupBaseER, which uses a different proprietary polymer-based vehicle than does the BupHClER formulation. Eighteen cynomolgus macaques (M. fascicularis) were divided into 2 groups. Each macaque in the first group (n = 6) received a single subcutaneous injection of 0.06 mg/kg BupBaseER (10 mg/mL) followed at least 2 wk later by a single subcutaneous injection of 0.12 mg/kg. Animals in group 2 (n = 12) received 2 injections of each of 3 compounds-the original polymer matrix vehicle used in BupHClER, the modified polymer matrix vehicle used in BupBaseER, and 0.9% saline-in designated areas of the dorsoscapular region. The 0.06- and 0.12-mg/kg doses both maintained therapeutic levels that were 3 times higher than the hypothesized analgesic threshold of 0.1 ng/mL. These doses maintained therapeutic level for approximately 44 and 103 h, respectively. Based on these data, buprenorphine concentration likely remains well above the therapeutic threshold beyond the 120 h span of this study. During the 30 d after administration, one macaque had a mild skin reaction to BupHClER. None of the animals in either group had skin reactions to BupBaseER at either dosage. These findings support the use of BupBaseER to provide pain management, promote animal welfare, decrease animal stress, and simplify the postoperative management of NHP in research and zoological settings.