Sublingual epinephrine tablets versus intramuscular injection of epinephrine: Dose equivalence for potential treatment of anaphylaxis - 16/08/11
Reprint requests: Keith J. Simons, PhD, Room 202, 50 Sifton Road, Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada, R3T 2N2.Winnipeg, Manitoba, Canada
Abstract |
Background |
Epinephrine autoinjectors are underused in the emergency treatment of anaphylaxis in the community, perhaps in part because of fear of needles.
Objectives |
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 (Cmax), and time at which Cmax was achieved (Tmax) did not differ significantly (P > .05) after epinephrine 40 mg (AUC = 1861 ± 537 ng/mL/min, Cmax = 31.0 ± 13.1 ng/mL, and Tmax = 9 ± 2 minutes) and epinephrine 0.3 mg intramuscular (AUC = 2431 ± 386 ng/mL/min, Cmax = 50.3 ± 17.1 ng/mL, and Tmax = 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.
Conclusion |
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.
Clinical implications |
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.
Le texte complet de cet article est disponible en PDF.Key words : Epinephrine, adrenaline, sublingual tablet, sublingual absorption, EpiPen, anaphylaxis, systemic allergic reaction
Abbreviations used : AUC, Cbaseline, Cmax, Tmax
Plan
| Disclosure of potential conflict of interest: F.E.R. Simons is on the advisory board of Dey and Verus. K.J. Simons is on the advisory board for Verus. M.M. Rawas-Qalaji has no conflict of interest to disclose. |
Vol 117 - N° 2
P. 398-403 - février 2006 Retour au numéro
Article précédent
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