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

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 ( 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.

An Examination of the Complex Pharmacological Properties of the Non-Selective Opioid Modulator Buprenorphine

“…Buprenorphine brings about mild respiratory depression, whereas at high doses fentanyl causes significant respiratory depression and apnea [145]. Although buprenorphine has been observed to cause partial respiratory depression, the results indicate that administration of buprenorphine buccal film may have a decreased risk of abuse and respiratory depression compared with the full MOR agonist oxycodone [146].…”

“…In 2019, an expert panel provided clinical recommendations for discussing buprenorphine for chronic pain. Buccal film and transdermal formulations of buprenorphine are indicated for pain management for conditions that require daily, continuous opioid treatment [146]. Patients with chronic pain may benefit from buprenorphine if they have an increased risk of adverse events typically relating to opioids, including those suffering from obstructive sleep apnea, a comorbid psychiatric diagnosis, pulmonary disease, or those who have a high body mass index [146].…”

Frontline Perspectives on Buprenorphine for the Management of Chronic Pain

“… 48 A Phase 1 study comparing BBF with IR oxycodone suggests that BBF leads to decreased risk of abuse and respiratory depression compared with full µ-OR agonists. 52 Buprenorphine has a favorable safety profile, as demonstrated by studies showing a ceiling effect on respiratory depression and gastrointestinal adverse events compared with other opioid treatments and formulations. 36 , 53 , 54 Consequently, the US Department of Health and Human Services recommends encouraging the Centers for Medicare & Medicaid Services and private payers to provide coverage and reimbursement for buprenorphine in patients with chronic pain.…”