Epinephrine Absorption in Children With a History of Anaphylaxis

Abstract

Simons FER, Roberts JR, Gu A, Simons KJJ Allergy Clin Immunol.10119983337To study the clinical pharmacology of epinephrine in allergic children with a history of anaphylaxis.A total of 17 children, ages 4 to 12 years old, with a history of severe allergies and systemic anaphylaxis.This was a randomized, single-blind, single-dose, parallel-group study. Subjects received either a subcutaneous injection of 0.01 mL/kg (maximum 0.3 ml [0.3 mg]) epinephrine solution or an intramuscular injection of 0.3 mL (0.3 mg) of epinephrine via an EpiPen Auto-Injector (Dey; Napa, CA). Before injection and at timepoints up to 180 minutes afterwards, blood samples were collected for plasma epinephrine measurement. Heart rate, blood pressure, and rhythm strip monitoring were also performed during the same intervals. Plasma epinephrine concentrations were measured with a high-performance chromatography (HPLC) reverse-phase system with electrochemical detection.Nine subjects were randomized to the subcutaneous epinephrine group (epinephrine solution) and 8 to the intramuscular injection group (EpiPen Auto-Injector). The mean peak plasma epinephrine concentration in the subcutaneous group was 1802 ± 214 pg/mL. The mean time to reach maximum plasma concentrations was 34 ± 14 minutes in this group, with only 2 subjects achieving maximum concentration by 5 minutes. In contrast, the mean peak maximum plasma epinephrine concentration in the intramuscular group was 2136 ± 351 pg/mL. The mean time to reach maximum plasma concentration was 8 ± 2 minutes (P < .05, compared to subcutaneous group), with 6 achieving the peak concentration by 5 minutes. No serious adverse effects were reported in either group.Epinephrine has a delayed absorption when given via the subcutaneous route compared with the intramuscular route in children.Although a small sample size, this study of the pharmacologic dynamics of epinephrine delivery in children has great implications. Epinephrine remains the drug of choice for the treatment of acute systemic anaphylaxis, yet epinephrine dosing in children is currently recommended on the basis of findings in adult populations and anecdotal reports. This study is the first to demonstrate the pharmacokinetics of epinephrine in children. The authors clearly demonstrate delayed absorption and lower peak plasma concentrations when epinephrine is given via the subcutaneous route compared with the intramuscular route. These findings have important clinical implications for use of epinephrine in all settings of systemic anaphylaxis, indicating that intramuscular delivery of epinephrine may be preferable.