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

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.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.