5-Period, 5-Treatment Crossover Study to Compare the Pharmacokinetics of Intranasal and Intramuscular Epinephrine Administration in Healthy Adult Participants

Intramuscular (IM) epinephrine via autoinjector has suboptimal compliance/use; alternatives are needed. We compared bioavailability and cardiovascular effects of intranasal (IN) nasal spray versus IM epinephrine. This open-label, randomized, 5-treatment, 5-way crossover study included 25 healthy participants aged 19–45 years. Epinephrine administrations were: 6.6-mg IN (1x6.6-mg), 4.4-mg (2x2.2-mg), 8.8-mg (2x4.4-mg), 13.2-mg (2x6.6-mg), 0.3-mg (1x0.3-mg); second administration within 10 seconds after first dose (opposite nostril); ≥1 day washout. concentrations were measured (-30–360 minutes). PK parameters (AUC0–10, AUC0–20, AUC0–30, AUC0–60, AUC0–360, Cmax(10 min), Cmax; ANOVA analysis) safety assessed. Aside from AUC0-10, AUCs Cmax values greater 936 vs 979 min*pg/mL; 3054 2273 5291 3756 10171 7433 25461 15163 277 246; Cmax, 293 238 pg/mL). After 20 minutes, baseline-corrected ≥100 pg/mL reached by 100% (13.2-mg IN), 80% (6.6-mg IN, IM), 60% (4.4-mg IN) participants; ≥200 64% 56% (8.8-mg 32% participants. had no clinically meaningful heart rate/blood pressure effects. cumulative data demonstrate that the single was comparable to or than autoinjector, with similar