Sublingual epinephrine tablets versus intramuscular injection of epinephrine: dose equivalence for potential treatment of anaphylaxis.
BACKGROUND
Epinephrine autoinjectors are underused in the emergency treatment of anaphylaxis in the community, perhaps in part because of fear of needles.


OBJECTIVE
To determine the sublingual epinephrine dose from a novel fast-disintegrating tablet required to achieve epinephrine plasma concentrations (EPPCs) similar to those obtained after epinephrine 0.3 mg intramuscular injection.


METHODS
In a prospective 5-way crossover study, sublingual tablets containing epinephrine 0, 10, 20, and 40 mg, and epinephrine 0.3 mg intramuscular in the thigh (EpiPen) were compared in a validated rabbit model. Blood samples were collected before dosing and 5, 10, 15, 20, 30, 40, 60, 90, 120, 150, and 180 minutes afterward. EPPCs were measured by using high-performance liquid chromatography-electrochemical detection. Pharmacokinetic parameters were calculated by using WinNonlin.


RESULTS
The area under the curve (AUC), maximum concentration (C(max)), and time at which C(max) was achieved (T(max)) did not differ significantly (P > .05) after epinephrine 40 mg (AUC = 1861 +/- 537 ng/mL/min, C(max) = 31.0 +/- 13.1 ng/mL, and T(max) = 9 +/- 2 minutes) and epinephrine 0.3 mg intramuscular (AUC = 2431 +/- 386 ng/mL/min, C(max) = 50.3 +/- 17.1 ng/mL, and T(max) = 21 +/- 5 minutes). The AUC after tablets containing epinephrine 0 mg (AUC = 472 +/- 126 ng/mL/min), epinephrine 10 mg (AUC = 335 +/- 152 ng/mL/min), and epinephrine 20 mg (AUC = 801 +/- 160 ng/mL/min) did not differ significantly from each other, but were significantly lower (P < .05) than the AUC after epinephrine 0.3 mg intramuscularly.


CONCLUSIONS
Sublingual administration of epinephrine 40 mg from this tablet formulation resulted in EPPCs similar to those obtained after epinephrine 0.3 mg intramuscular injection in the thigh.


CONCLUSIONS
For treatment of anaphylaxis in the community, self-injectable epinephrine is underused. This novel, fast-disintegrating epinephrine tablet formulation for sublingual administration is a feasible alternative that warrants further development.
Rawas-Qalaji
Mutasem M
MM
Faculty of Pharmacy, University of Manitoba, Canada.
Simons
F Estelle R
FE
Simons
Keith J
KJ
D000286:Administration, Sublingual; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004837:Epinephrine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007273:Injections, Intramuscular; D011446:Prospective Studies; D011817:Rabbits; D013607:Tablets
D000318:Adrenergic beta-Agonists; D013607:Tablets; D004837:Epinephrine