Pharmacokinetics, Safety and Tolerability of Inhaled Epinephrine from Cyclops™ in Healthy Volunteers

Floris Grasmeijer^1,2, Wouter Dijkstra¹, Reinier Schwietert¹ & Erik Frijlink²

¹PureIMS B.V., Ceintuurbaan Noord 152, Roden, 9301 NZ, the Netherlands

²Department of Pharmaceutical Technology & Biopharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, the Netherlands

Summary

Intramuscular administration of epinephrine by autoinjectors is prone to errors and associated with a high barrier to use. Epinephrine dry powder inhalation may offer a more convenient, low-barrier alternative. Therefore, the pharmacokinetics, safety and tolerability of an epinephrine dry powder inhalation formulation administered with the single-use inhaler Cyclops™ was determined in this phase I, ascending-dose, placebo-controlled crossover study. Inhaled epinephrine in nominal doses of 0.35, 0.65 and 1.3 mg was well tolerated by ten healthy volunteers as no cough or local irritation was observed and no systemic reactions occurred. The T_max of inhaled epinephrine was 2 minutes versus 34 minutes following intramuscular administration of epinephrine with an autoinjector. The mean C_max was four-fold higher after inhalation of 1.3 mg of epinephrine than after 0.3 mg intramuscular epinephrine, whereas the mean total exposure in the first 30 min (AUC0-30) was comparable. This study therefore demonstrates the potential of inhaled epinephrine as a first-line treatment in the event of an emerging allergic reaction.

Key Message

Inhaled epinephrine from Cyclops™ was well-tolerated by healthy volunteers and rapidly systemically absorbed. Effective epinephrine peak plasma concentrations were measured within 5 minutes after inhalation, which demonstrates the potential of Epinephrine Cyclops™ as a first-line treatment in the event of an emerging allergic reaction.