A preliminary study of intranasal epinephrine administration as a potential route for anaphylaxis treatment

The intranasal (IN) administration of epinephrine could be an alternative route for anaphylaxis treatment. Although IN epinephrine absorption has been demonstrated in animals, such data in humans are still lacking.

To study the pharmacokinetics of IN epinephrine absorption in humans.

Each healthy adult (n = 5) was administered IN saline, IN epinephrine at various doses (i.e., 0.3, 0.6, 1.25, 2.5 and 5 mg), and intramuscular (IM) epinephrine at 0.3 mg. Plasma epinephrine levels at baseline and various time points up to 120 minutes after administration were determined using high-performance liquid chromatography with electrochemical detection.

Significant systemic absorption of epinephrine via IN route was observed only at the dose of 5 mg, and the absorption thereof was comparable to that of IM epinephrine; the average area-under-curve (AUC) values at 0-120 minutes for IN saline, IM epinephrine, and 5 mg IN epinephrine were 0.3, 18.3, and 19.4 ng.min/mL, respectively. In addition, the peak epinephrine concentrations and the time to reach them were also not significantly different between IM and 5-mg IN epinephrine; the corresponding values (mean ± SD) were 309 ± 88 pg/mL and 67 ± 43 min for IM epinephrine, and 386 ± 152 pg/mL and 70 ± 17 min for 5 mg IN epinephrine.

This preliminary study showed that epinephrine can be significantly absorbed via the IN route in humans. However, it requires a higher IN dose (5 mg) than the usual IM dose (0.3 mg) to achieve comparable systemic epinephrine absorption.