Bioequivalence evaluation of epinephrine autoinjectors with attention to rapid delivery

Abstract

Timely and proper injection of epinephrine is critical to prevent serious consequences relating to anaphylaxis. In a recent bioavailability study comparing epinephrine delivery from the Auvi-Q™ and EpiPen^® epinephrine autoinjectors, the Auvi-Q failed to meet the bioequivalence threshold when using partial area under the curve (AUC) analyses based on zero to T_max recommended for highly variable drugs such as epinephrine. Peak plasma epinephrine concentrations for the EpiPen occurred 10 minutes (median T_max) after dosing, while peak concentrations for the Auvi-Q occurred 20 minutes after dosing. Though bioequivalence may be concluded for C_max, AUC_inf, and AUC_0–t, for fast-acting therapeutics used to treat life-threatening conditions, such as epinephrine, additional pharmacokinetic parameters such as AUC zero to T_max may be important to evaluate when assessing bioequivalence.

Keywords:

• anaphylaxis
• therapy
• pharmacokinetics
• bioavailability
• EpiPen
• T_max

Acknowledgment

Editorial support was provided by Rebecca E Slager, PhD, MS, at MedThink SciCom.

Disclosure

Editorial support was funded by Mylan Specialty LP (Basking Ridge, NJ, USA). Dr Sclar has served as a consultant to Mylan Specialty LP.