Pharmacokinetic and Pharmacodynamic Comparison of Epinephrine administered intranasally and intramuscularly: an integrated analysis.

BACKGROUND: Manual intramuscular epinephrine injection is the standard of care for treating severe allergic reactions and anaphylaxis. Epinephrine autoinjectors were approved based on the assumption that their pharmacokinetic and pharmacodynamic profiles are equivalent to manual intramuscular injection, however while there is emerging evidence for product-related differences in pharmacokinetic profiles, very little is known about the comparative pharmacodynamic profiles.

OBJECTIVE: To compare pharmacokinetic and pharmacodynamic profiles of epinephrine delivered via manual intramuscular injection, autoinjectors, and intranasal spray.

METHODS: This integrated analysis was based on data from four randomized cross-over phase 1 trials that compared the pharmacokinetics and pharmacodynamics of epinephrine using manual intramuscular epinephrine 0.3 mg injection, epinephrine 0.3 mg autoinjectors (EpiPen ®) and epinephrine 1 mg intranasal spray (neffy TM).

RESULTS: Data from 175 participants demonstrated that although neffy (1.0 mg intranasal spray) resulted in a lower or comparable maximum concentration (258 pg/mL) versus manual epinephrine intramuscular injection (254 pg/mL) and EpiPen (503 pg/mL), it led to comparable increases in systolic blood pressure (maximum effect [E max], 16.9, 10.9, 14.9, and 18.1 mm Hg, respectively). neffy's effect on diastolic blood pressure was also markedly more pronounced compared to other products (E max, 9.32, 5.51, 5.78 and 5.93 mm Hg, respectively).

CONCLUSION: Intranasal delivery of epinephrine using neffy increases systolic blood pressure more efficiently compared with manual intramuscular injection and epinephrine autoinjectors, despite lower maximum plasma concentrations.