Indivior Study Shows Buprenorphine May Mitigate Fentanyl-Induced Respiratory Depression In Chronic Opioid Users

Indivior PLC  INVVY INDV published modeling data examining the competitive interaction between buprenorphine, a treatment for opioid use disorder, and fentanyl, a potent synthetic opioid, to better understand how buprenorphine can reduce fentanyl-induced respiratory depression. The study entitled "Modelling buprenorphine reduction of fentanyl-induced respiratory depression" is available online and will appear in an upcoming print issue of JCI Insight, a peer-reviewed journal. The study was supported by Indivior.

This pharmacokinetic/pharmacodynamic study aimed at modeling the interaction of buprenorphine and fentanyl at the level of the mu-opioid receptor on minute ventilation under elevated carbon dioxide levels in opioid-naïve volunteers and chronic opioid users. Data used for modeling were from a clinical pharmacology study recently published in PLOS ONE. The main objective of the modeling was to characterize the effects of escalating intravenous fentanyl doses (0.25-0.70 mg/70 kg range in chronic opioid users) on respiratory depression compared to the intravenous infusion of either placebo or buprenorphine targeting plasma concentrations within the 0.2-5 ng/mL range.

Buprenorphine medications for opioid use disorder has been shown to reduce illicit opioid use and opioid-related mortality. This analysis describes another mechanism by which buprenorphine may reduce opioid overdose deaths. The modeling data indicate that buprenorphine plasma concentrations of 2 ng/mL and higher may have a protective effect against fentanyl-induced respiratory depression in chronic opioid users, with a reduced probability of apnea following exposure to high fentanyl doses. The model shows that when MOR occupancy by buprenorphine is sufficiently high, fentanyl is unable to activate the MOR and consequently will not cause additional respiratory depression on top of the mild respiratory effects of buprenorphine in that population.

"These modeling data show that buprenorphine plasma concentrations of 2 ng/mL and higher seem to have a protective effect against fentanyl-induced respiratory depression," stated Christian Heidbreder, PhD, chief scientific officer, Indivior. "Although the source study was conducted in a controlled setting and in a relatively small number of chronic opioid users, the ability of buprenorphine to reduce the risk of serious respiratory events triggered by fentanyl was demonstrated and warrants further investigation in a real-world setting."

Photo: Courtesy of Vladislav Muslakov on Unsplash

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