Pharmacokinetics of a Transdermal Buprenorphine Topical Solution in the Cynomolgus Macaque (Macaca fascicularis).

Abstract

Pain management is an expansive and ever-evolving component of managing nonhuman primates in the research setting. Opioids are a commonly used analgesic medication and are available in a variety of formulations. A novel, long-acting transdermal buprenorphine topical solution was recently approved for use in cats to provide up to 4 days of postoperative analgesia. The purpose of this study was to evaluate the pharmacokinetic profile of this transdermal formulation in cynomolgus macaques. Five male cynomolgus macaques were used in a 2-formulation crossover study to compare the pharmacokinetics of a single transdermal dose (20 mg) to a single intravenous dose of buprenorphine HCl (0.01 mg/kg). Plasma buprenorphine levels were measured for animals receiving transdermal buprenorphine topical solution at time points 0 (baseline), 1, 3, 6, 12, 24, 36, 48, 72, 96, and 120 hours postdosing. Plasma buprenorphine levels were measured for animals receiving intravenous buprenorphine at time points 0 (baseline), 2, 5, 10, 25, 45, and 60 minutes and at 3, 6, 12, and 24 hours postdosing. Animals weighing 3.55-6.2 kg reached therapeutic plasma levels, as hypothesized in the literature (0.1 ng/mL), within 1 hour of administration and maintained therapeutic levels for at least 72 hours. This study demonstrates that this novel transdermal buprenorphine topical solution can offer a refinement in pain management of nonhuman primates through a less invasive route of administration with an extended duration of action.