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

Lynn R Webster, Jacqueline Cater, Thomas Smith, Lynn R Webster, Jacqueline Cater, Thomas Smith

Abstract

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 (Tmax) 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 (Cmax) was 1.06 ng/mL for 900 µg BBF and 132 ng/mL for 60 mg oxycodone. The abuse quotient, defined as Cmax/Tmax, 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.

Keywords: Abuse quotient; Buprenorphine; Oxygen saturation; Pharmacokinetics.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study design. BBF indicates buprenorphine buccal film; oxy, oxycodone. Reproduced from Webster et al. [22], under the CC BY-NC 4.0 Open Access License
Fig. 2
Fig. 2
Mean (± SD) plasma concentration of a buprenorphine and b oxycodone over time, (N = 19)
Fig. 3
Fig. 3
Mean (± SD) oxygen saturation in response to BBF and oxycodone administration, (N = 15). BBF indicates buprenorphine buccal film; Oxy oxycodone. Consort flowchart and checklist: not applicable because the primary results of the study were already published; this report focuses on a secondary analysis

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