LB-011 - THE EFFECT OF NASAL CONGESTION ON THE BIOAVAILABILITY OF INTRANASALLY ADMINISTERED EPINEPHRINE IN HEALTHY ADULT SUBJECTS WITH SEASONAL ALLERGIES.

A. van Haarst¹, A. Hunt², Z. Machnes³, M. Di Spirito³, M. Lor³, D. Dworaczyk⁴; ¹Celerion, Belfast, United Kingdom, ²Celerion, Lincoln, NE, United States, ³Celerion, Montreal, QC, Canada, ⁴Bryn Pharma, LLC., Raleigh, NC, United States.

Background: Intramuscular (IM) administration of epinephrine is a first-line treatment of anaphylaxis. Intranasal (IN) epinephrine may offer a faster route of administration avoiding reluctance to IM injection and application error, yet nasal congestion may affect IN absorption.

Methods: In an open-label, 4-period study, 51 subjects with seasonal allergy received a single IN dose of 13.2 mg epinephrine (given in 2 consecutive sprays), with and without nasal congestion, as well as a single IM epinephrine injection by 2 modalities (0.3 mg by EpiPen® and 0.5 mg by manual syringe). IN sprays were administered in opposite nostrils. A nasal allergen challenge was performed to establish nasal congestion prior to IN dosing. Washout between IN epinephrine dosings was ≥ 14 days. Blood samples were collected and blood pressure and heart rate were measured out to 360 minutes postdose. Pharmacokinetic parameters included AUC0-360, Cmax, Tmax.

Results: Geometric means for baseline-adjusted epinephrine AUC0-360 and Cmax for 13.2 mg IN were 34200 pg•min/mL and 458.0 pg/mL (with congestion) and 29680 pg•min/mL and 270.1 pg/mL (without congestion); the 70% increase in Cmax was significant. Following 0.5 mg and 0.3 mg IM doses, AUC0-360 were 32400 and 16710 pg•min/mL, and Cmax were 364.2 and 279.0 pg/mL, respectively. Median Tmax were 15.1, 25.2, 45.0 and 21.5 minutes after IN dosing with and without congestion and after 0.5 mg and 0.3 mg IM dosing, respectively. Cardiovascular effects mirrored epinephrine levels. There were no serious or unexpected adverse effects.

Conclusion: Nasal congestion enhances peak levels of IN epinephrine. Exposure after 13.2 mg IN epinephrine (with and without nasal congestion), however, was similar to that after 0.5 mg IM epinephrine by manual syringe, but greater than for the 0.3 mg IM dose (EpiPen®).