Is epinephrine administration by sublingual tablet feasible for the first‐aid treatment of anaphylaxis? A proof‐of‐concept study

Purpose : In order to explore the feasibility of sublingual administration of epinephrine tablets as a non‐invasive first‐aid treatment for anaphylaxis, we studied epinephrine absorption from this dosage form in an animal model. Methods : In a prospective, randomized, four‐way crossover study, six rabbits received epinephrine 2.5 or 10 mg as a sublingual tablet, epinephrine 0.03 mg (0.3 ml) by intramuscular (IM) injection (positive control), and 0.9% NaCl (0.3 ml) IM (negative control). Pre‐ and post‐dose blood samples were obtained for measurement of plasma epinephrine concentrations by HPLC‐EC. Results : After administration of epinephrine 2.5 mg as a sublingual tablet, the mean (±SEM) C max was 2369±392 pg/ml, and the t max was 20.8±5.7 min. After administration of epinephrine 10 mg sublingually, the C max was 10836±2234 pg/ml, and the t max was 21.7±5.4 min. After IM epinephrine, the C max was 6445±4233 pg/ml, and the t max was 15.8±4.7 min. After IM 0.9% NaCl, the C max (endogenous epinephrine) was 518±142 pg/ml. The t max after both of the sublingual epinephrine tablet doses did not differ significantly from the t max after IM epinephrine, and the C max after the 10 mg sublingual epinephrine tablet dose did not differ significantly from the C max after IM epinephrine. Conclusions : In this proof‐of‐concept study, administration of epinephrine as a sublingual tablet formulation resulted in rapid achievement of peak plasma epinephrine concentrations. Absorption studies in humans are needed. Definitions: HPLC—high performance liquid chromatography; EC — electrochemical detection; C max — maximum plasma epinephrine concentration after dosing; t max — time of maximum plasma epinephrine concentration. Copyright © 2002 John Wiley & Sons, Ltd.