Pharmacokinetics of Buprenorphine Buccal Film and Orally-administered Oxycodone in a Respiratory Study: An Analysis of Secondary Outcomes from a Randomized Controlled Trial

OBJECTIVE: To evaluate pharmacokinetic (PK) parameters and oxygen saturation as markers of abuse potential after administration of buprenorphine buccal film (BBF) and immediate-release (IR) oxycodone. METHODS: This was a secondary analysis of data from a phase I randomized controlled trial. A total of 19 healthy subjects who self-identified as recreational opioid users were enrolled, with 15 completing the study. Subjects were administered 300, 600, and 900 µg BBF; 30 and 60 mg orally-administered oxycodone; and placebo. For PK analysis, blood samples were collected before dosing and at 0.5, 1, 2, 3, 4, and 6 h postdose. Respiratory drive/ventilatory response to hypercapnia and oxygen saturation were evaluated before dosing and up to 8 h after administration of test drugs. RESULTS: Median time to maximum concentration (T(max)) was 2.17 h for 900 µg BBF and 1.17 h for 60 mg oxycodone and was similar across all doses for each drug. Mean maximum concentration (C(max)) was 1.06 ng/mL for 900 µg BBF and 132 ng/mL for 60 mg oxycodone. The abuse quotient, defined as C(max)/T(max), was substantially higher for oxycodone compared to BBF. Respiratory depression (maximum decrease in minute ventilation) was similar for all 3 doses of BBF, consistent with a potential ceiling effect. In addition, respiratory depression occurred sooner with oxycodone vs BBF, and a greater mean decrease in oxygen saturation was observed for oxycodone 30- and 60-mg doses, compared with BBF. CONCLUSION: These results indicate that BBF may have a decreased risk of abuse and respiratory depression compared with the full µ-opioid receptor agonist oxycodone. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03996694.