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


BACKGROUND
HPLC-high performance liquid chromatography; EC - electrochemical detection; C(max) - maximum plasma epinephrine concentration after dosing; t(max) - time of maximum plasma epinephrine concentration.
Gu
Xiaochen
X
Assistant Professor, Division of Pharmaceutical Sciences, Faculty of Pharmacy, University of Manitoba, Canada R3T 2N2.
Simons
Keith J
KJ
Simons
F Estelle R
FE
D000286:Administration, Sublingual; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D018592:Cross-Over Studies; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005392:First Aid / Q000379:methods*; D007273:Injections, Intramuscular; D011446:Prospective Studies; D011817:Rabbits; D013607:Tablets
D000318:Adrenergic beta-Agonists; D013607:Tablets; D004837:Epinephrine