A 13.2 mg epinephrine intranasal spray demonstrates comparable pharmacokinetics, pharmacodynamics, and safety to a 0.3 mg epinephrine autoinjector

David A Dworaczyk; Allen L Hunt; Mike Di Spirito; Mary Lor; Kenneth L Dretchen; Michael J Lamson; Jonathan Pollock; Thelma Ward

doi:10.1016/j.jacig.2023.100200

A 13.2 mg epinephrine intranasal spray demonstrates comparable pharmacokinetics, pharmacodynamics, and safety to a 0.3 mg epinephrine autoinjector

J Allergy Clin Immunol Glob. 2023 Dec 12;3(2):100200. doi: 10.1016/j.jacig.2023.100200. eCollection 2024 May.

Authors

David A Dworaczyk¹, Allen L Hunt², Mike Di Spirito², Mary Lor², Kenneth L Dretchen³, Michael J Lamson⁴, Jonathan Pollock², Thelma Ward²

Affiliations

¹ Bryn Pharma LLC, Raleigh, NC.
² Celerion Inc, Lincoln, Neb.
³ Mesa Science Associates, Frederick, Md.
⁴ Allucent, Cary, NC.

Abstract

Background: Recent acute anaphylaxis guideline updates have identified remaining unmet needs based on currently available therapeutic options as a critical focus.

Objective: We compared the pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of intranasal epinephrine with intramuscular epinephrine administered by autoinjector and manual syringe.

Methods: An open-label, 3-period crossover study was conducted in 116 healthy adult volunteers to assess the bioavailability of a single 13.2 mg intranasal dose of epinephrine compared to a 0.3 mg intramuscular autoinjector and a 0.5 mg manual syringe. Patients with epinephrine concentrations of 50, 100, and 200 pg/mL at 10, 20, 30, and 60 minutes after dosing were also evaluated.

Results: Pharmacokinetic parameters for the 13.2 mg intranasal dose exceeded those of the 0.3 mg autoinjector with a rapid and higher maximum observed concentration (intranasal, 429.4 pg/mL; autoinjector, 328.6 pg/mL) and greater systemic exposure (AUC_0-360; intranasal, 39,060 pg∙min/mL; autoinjector, 17,440 pg∙min/mL). Similar results were observed compared to the 0.5 mg manual syringe. Pharmacokinetic parameters for opposite-nostril and same-nostril dosing were higher than both intramuscular doses, except time to reach maximum observed concentration, which was bracketed between the 2 intramuscular doses (intranasal opposite and same nostril, 20 minutes; autoinjector, 14.9 minutes; manual syringe, 45 minutes). Similar effects on blood pressure and heart rate were observed for intranasal and autoinjector administration. Intranasal epinephrine was safe and well tolerated. No serious or unexpected adverse events were reported, confirming results from earlier clinical studies.

Conclusions: Bidose epinephrine spray addresses the unmet medical and patient needs for a needle-free, convenient, and effective dose-delivery system for self-administration of epinephrine that is as good as or better than the 0.3 mg autoinjector.

Keywords: Anaphylaxis; Bryn Pharma; NDS1C; delivery system; epinephrine; food allergy; intranasal; pharmacodynamics; pharmacokinetics; self-administration; venom allergy.