A pharmacokinetic study of extended-release buprenorphine in cynomolgus monkeys (Macaca fasicularis).

Abstract

A novel buprenorphine (BUP) extended-release formulation (BUP-XR) produced as a lipid-encapsulated, low viscosity BUP suspension for subcutaneous (SC) injection to control pain was evaluated for pharmacokinetics and safety in four adult male cynomolgus monkeys. Each animal was given 0.2 mg/kg reformulated BUP-XR SC. Clinical observations were made during the course of the study. Blood samples were obtained from each animal before BUP-XR administration, 6, 24, 48, 72, and 96 h post-BUP-XR injection. Plasma levels of buprenorphine were analyzed using HPLC-MS/MS. The PK values calculated included peak plasma concentration of the BUP analyte, time to peak plasma concentration, plasma half-life, area under the plasma concentration-time curve, clearance, apparent volume of distribution, and elimination rate constant (Cmax , Tmax , T½ , AUC0-t , CL, Vd, and Ke, respectively). Observable adverse clinical signs were not detected. BUP concentration peaked from 6 to 48 h, then declined in a linear fashion. Quantifiable plasma BUP was measured in all monkeys at all time points. Results indicate that a single BUP-XR dose at 0.2 mg/kg can reliably provide plasma levels of BUP reported in the literature to be therapeutically relevant for up to 96 h. Because of the lack of any clinical observations or adverse effects at the injection site or absence of observable abnormal behaviors, it may be concluded that the use of BUP-XR is safe and efficacious in this species of non-human primate at the dose regimen described in this study for up to 96 h post-administration.