Pharmacokinetic and pharmacodynamic profile of epinephrine nasal spray versus intramuscular epinephrine auto-injector in healthy adults

Authors

Matthew Greenhawt, Section of Allergy and Immunology, Children's Hospital Colorado, Department of Pediatrics, University of Colorado School of Medicine, Denver, CO, USA. Electronic address: Matthew.Greenhawt@childrenscolorado.org.
Jay Lieberman, The University of Tennessee Health Science Center, Memphis, TN, USA.
Michael Blaiss, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
David I. Bernstein, Division of Immunology and Allergy, University of Cincinnati College of Medicine and Bernstein Clinical Research Center, Cincinnati, OH, USA.
John Oppenheimer, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey-Rutgers New Jersey Medical School, Newark, NJ, USA.
Lawrence DuBuske, Department of Medicine, The George Washington University Hospital, Washington, D.C., USA.
David Fleischer, Section of Allergy and Immunology, Children's Hospital Colorado, Department of Pediatrics, University of Colorado School of Medicine, Denver, CO, USA.
David A. Dworaczyk, Bryn Pharma, LLC, Lebanon, NJ, USA.

Document Type

Journal Article

Publication Date

10-10-2024

Journal

The journal of allergy and clinical immunology. In practice

DOI

10.1016/j.jaip.2024.10.006

Keywords

anaphylaxis; epinephrine; intranasal; pharmacodynamics; pharmacokinetics

Abstract

BACKGROUND: Standard of care for anaphylaxis treatment is intramuscular (IM) epinephrine. An epinephrine nasal spray (ENS) is under development as an alternative form of administration. OBJECTIVE: To compare the pharmacokinetic (PK) and pharmacodynamic (PD) profile of 13.2 mg ENS with 0.3 mg IM epinephrine auto-injector. METHODS: Data from 4 open-label phase 1 crossover studies conducted in healthy adults were pooled to determine the PK and PD profile of a single 13.2 mg ENS dose delivered by 2 consecutive sprays of 6.6 mg each in opposite (n=224 doses) or the same nostril (n=75 doses) compared with the 0.3 mg IM auto-injector (n=215 doses). Each participant served as their own control. Blood samples and vital signs were collected pre-dose and at multiple intervals from 0-360 minutes post-dose. RESULTS: ENS rapidly increased the plasma epinephrine concentration, with levels that were overall greater than IM auto-injector. Median (range) time to maximum plasma epinephrine concentration with ENS opposite nostrils, ENS same nostril, and IM auto-injector was 25.1 (1.3, 362.1), 20.1 (3.0, 120.2), and 20.0 (1.0, 121.3) minutes, respectively. The area under the plasma concentration-time curve for 0-360 minutes was significantly higher with ENS than the IM auto-injector (geometric mean ratio [90% CI]=155% [140%, 172%] with ENS opposite nostrils, 159% [138%, 182%] with ENS same nostril). The PD effects on heart rate and blood pressure were similar in pattern and magnitude among all 3 treatment groups. CONCLUSIONS: ENS rapidly achieved plasma epinephrine levels greater and more sustained than the IM auto-injector and with a similar PD effect.

APA Citation

Greenhawt, Matthew; Lieberman, Jay; Blaiss, Michael; Bernstein, David I.; Oppenheimer, John; DuBuske, Lawrence; Fleischer, David; and Dworaczyk, David A., "Pharmacokinetic and pharmacodynamic profile of epinephrine nasal spray versus intramuscular epinephrine auto-injector in healthy adults" (2024). GW Authored Works. Paper 5850.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5850

Department

Medicine