Sublingual epinephrine tablets versus intramuscular injection of epinephrine: dose equivalence for potential treatment of anaphylaxis.

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 (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.

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.

• Authors: Mutasem M Rawas-Qalaji, F Estelle R Simons, Keith J Simons
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 117 Issue 2 Pg. 398-403 (Feb 2006) ISSN: 0091-6749 [Print] United States
• PMID: 16461140 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Adrenergic beta-Agonists
• Tablets
• Epinephrine

Topics

• Administration, Sublingual
• Adrenergic beta-Agonists (administration & dosage, pharmacokinetics, therapeutic use)
• Anaphylaxis (drug therapy)
• Animals
• Biological Availability
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Epinephrine (administration & dosage, pharmacokinetics, therapeutic use)
• Injections, Intramuscular
• Prospective Studies
• Rabbits
• Tablets