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Indivior Publishes Modeling Data Showing Buprenorphine May Mitigate Fentanyl-Induced Respiratory Depression in Chronic Opioid Users

Data available online and in an upcoming print issue of JCI Insight, a peer-reviewed journal

Richmond, VA, April 8, 2022 - Indivior PLC (LON: INDV) announces the publication of modeling data examining the competitive interaction between buprenorphine, a treatment for opioid use disorder (OUD), and fentanyl, a potent synthetic opioid, to better understand how buprenorphine can reduce fentanyl-induced respiratory depression.1 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 (MOR) on minute ventilation under elevated carbon dioxide levels in opioid-naïve volunteers and chronic opioid users.1 Data used for modeling were from a clinical pharmacology study recently published in PLOS ONE.2 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.1

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.1 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.1 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.1

“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,” said 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.”1

Read full study here.


About Opioid Use Disorder (OUD)

Opioid Use Disorder (OUD) is a chronic disease in which people develop a pattern of using opioids that can lead to negative consequences.3 OUD may affect the parts of the brain that are necessary for life-sustaining functions.3

About Indivior

Indivior is a global pharmaceutical company working to help change patients’ lives by developing medicines to treat substance use disorders (SUD) and serious mental illnesses. Our vision is that all patients around the world will have access to evidence-based treatment for the chronic conditions and co-occurring disorders of SUD. Indivior is dedicated to transforming SUD from a global human crisis to a recognized and treated chronic disease. Building on its global portfolio of OUD treatments, Indivior has a pipeline of product candidates designed to both expand on its heritage in this category and potentially address other chronic conditions and co-occurring disorders of SUD, including alcohol use disorder and cannabis use disorder. Headquartered in the United States in Richmond, VA, Indivior employs more than 900 individuals globally and its portfolio of products is available in over 40 countries worldwide. Visit to learn more. Connect with Indivior on LinkedIn by visiting

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Indivior PLC (LON: INDV)

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  1. Olofsen, E, et al. Modelling buprenorphine reduction of fentanyl-induced respiratory depression. JCI Insights, March 22, 2022.
  2. Moss LM et al. (2022) Effect of Sustained High Buprenorphine Plasma Concentrations on Fentanyl-Induced Respiratory Depression: A Placebo-Controlled Crossover Study. PlosOne, Published online January 27, 2022.
  3. U.S. Department of Health and Human Services (HHS), National Institute on Drug Abuse, National Institutes of Health. Drugs, Brains, and Behavior: The Science of Addiction. HHS Publication No. (SMA) 18-5063PT5, Printed 2018.