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Relative potency of intravenous oxymorphone compared to other µ opioid agonists in humans — pilot study outcomes

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Abstract

Aims

Intravenous (IV) misuse of the µ opioid analgesic oxymorphone has caused significant public health harms; however, no controlled data on its IV abuse potential are available. The primary aims of this pilot study were to directly compare IV oxymorphone to IV oxycodone, morphine, and hydromorphone on a subjective measure of drug liking and to assess relative potency.

Methods

Participants (n = 6) with opioid use disorder, physical dependence, and current IV use completed this two-site, within-subject, double-blind, placebo-controlled, inpatient pilot study. During each session, one IV dose (mg/70 kg) was administered: oxymorphone (1.8, 3.2, 5.6, 10, 18, 32), hydromorphone (1.8, 3.2, 5.6, 10, 18), oxycodone (18, 32, 56), morphine (18, 32), and placebo. Data were collected before and for 6 h after dosing. Primary outcomes included safety/physiological effects, subjective reports of drug liking, and relative potency estimates.

Results

All active test drugs produced prototypical, dose-related µ opioid agonist effects (e.g., miosis). Oxymorphone was more potent than the comparator opioids on several measures, including drug liking and respiratory depression (p < 0.05). Across abuse-related subjective outcomes, oxymorphone was 2.3–2.8-fold more potent than hydromorphone and 12.5–14-fold more potent than oxycodone (p < 0.05).

Conclusions

Despite the relatively small sample size, this pilot study detected robust oxymorphone effects. Oxymorphone was far more potent than the comparator opioids, particularly on abuse potential outcomes. Overall, these findings may help explain surveillance reports that demonstrate, after adjusting for prescription availability, oxymorphone is injected at the highest frequency, relative to other prescription opioids.

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Acknowledgements

We wish to thank the staff at the University of Kentucky (UK) Center on Drug and Alcohol Research and the New York State Psychiatric Institute (NYSPI) Clinical Research Unit for research support: Ida Holt RN, Janet Murray RN, Claudia Tindall APRN, Andrea Woodson RN, Rebecca Abbott, Nur Ali, Nicholas Allwood, Ben Foote, Jocelyn Nichols, Lauren Noble, Victoria Vessels, and Vincent Woolfolk; the investigational pharmacists at UK Investigational Pharmacy, Dr. Seth Larkin and Dr. Thomas Lyman and NYSPI, Dr. Robert Jung and Dr. Lindsey Tesseyman for preparing study medication; and Dr. Samy-Claude Elayi and Dr. Ronnie Zeidan for patient support.

Funding

This study was funded by grants from the U.S. Food and Drug Administration (HHSF223201710119C [SDC]; HHSF223201710120C [SLW]) and the National Center for Advancing of Translational Sciences (UL1TR001998 [UK CTSA]).

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Authors and Affiliations

  1. Department of Behavioral Science, University of Kentucky, College of Medicine, 845 Angliana Avenue, Lexington, KY, 40508, USA

    Shanna Babalonis, Michelle R. Lofwall & Sharon L. Walsh

  2. Center on Drug and Alcohol Research, University of Kentucky, College of Medicine, 845 Angliana Avenue, Lexington, KY, 40508, USA

    Shanna Babalonis, Paul Nuzzo, Michelle R. Lofwall & Sharon L. Walsh

  3. Columbia University Irving Medical Center, New York, NY, USA

    Sandra D. Comer, Jermaine D. Jones, Jeanne Manubay & Robert A. Whittington

  4. New York State Psychiatric Institute, New York, NY, USA

    Sandra D. Comer, Jermaine D. Jones & Jeanne Manubay

  5. Department of Psychiatry, University of Kentucky, College of Medicine, Lexington, KY, USA

    Michelle R. Lofwall & Sharon L. Walsh

  6. Department of Anesthesiology, University of Kentucky, College of Medicine, Lexington, KY, USA

    Kevin W. Hatton

  7. Department of Pharmacology, University of Kentucky, College of Medicine, Lexington, KY, USA

    Sharon L. Walsh

  8. Department of Pharmaceutical Sciences, University of Kentucky, College of Pharmacy, Lexington, KY, USA

    Sharon L. Walsh

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  1. Shanna Babalonis
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  2. Sandra D. Comer
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  3. Jermaine D. Jones
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  4. Paul Nuzzo
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  5. Michelle R. Lofwall
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  7. Kevin W. Hatton
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  8. Robert A. Whittington
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  9. Sharon L. Walsh
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Contributions

Sandra Comer, Sharon Walsh, and Shanna Babalonis were responsible for the study concept and design. Jermaine Jones, Sandra Comer, Sharon Walsh, and Shanna Babalonis directly supervised all research procedures and the conduct of the study. Paul Nuzzo trained the staff at both sites, provided technical support services, supervised daily operations, and conducted data analyses. Michelle Lofwall and Jeanne Manubay were responsible for the medical care of the participants and conducted medical interviews and physical examinations, reviewed laboratory results, and assessed all adverse events. Michelle Lofwall, Jeanne Manubay, Kevin Hatton, and Robert Whittington designed the medical protocols. Kevin Hatton and Robert Whittington conducted physical examinations, provided on-site safety monitoring, and helped guide dose selection and safety discussions. Shanna Babalonis wrote the manuscript and all other authors provided critical revisions for important intellectual content.

Corresponding author

Correspondence to Shanna Babalonis.

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Conflict of interest

In the past three years, Sandra Comer has provided consulting and advisory board services to pharmaceutical and health services companies (Alkermes, Charleston Labs, Clinilabs, Collegium, Epiodyne, Mallinckrodt, Nektar, Opiant, Osmotica, Otsuka, Sun Pharma), her university has received research contracts from companies for drug-related research for which she serves as Principal or Co-Principal Investigator (Alkermes, BioXcel, Corbus, GoMedical, Intra-cellular Therapies, Lyndra, and Janssen), and she received honoraria for writing critical reviews for the World Health Organization. Sharon Walsh has served as a consultant or scientific advisor for Opiant Pharmaceuticals, Cerevel Therapeutics, AstraZeneca, Camurus, Otsuka, BrainsWay, Trevi Therapeutics, Summit Biosciences, and World Meds over the past 3 years on topics related to opioid use disorder and its treatment but not directly related to the topic of this report. Jermaine Jones is currently the recipient of an investigator-initiated grant from Merck Pharmaceuticals and has served as a consultant for Alkermes for the past 3 years. Shanna Babalonis, Michelle Lofwall, Kevin Hatton, Jeanne Manubay, Robert Whittington, and Paul Nuzzo have no conflicts to report related to this project.

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Babalonis, S., Comer, S.D., Jones, J.D. et al. Relative potency of intravenous oxymorphone compared to other µ opioid agonists in humans — pilot study outcomes. Psychopharmacology 238, 2503–2514 (2021). https://doi.org/10.1007/s00213-021-05872-1

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