Comparison of the Pharmacokinetic Properties of Naloxone Following the Use of FDA-Approved Intranasal and Intramuscular Devices Versus a Common Improvised Nasal Naloxone Device.

Abstract

For more than a decade, first responders and the general public have been able to treat suspected opioid overdoses using an improvised nasal naloxone device (INND) constructed from a prefilled syringe containing 2mg of naloxone (1mg/mL) attached to a mucosal atomization device. In recent years, the U.S. Food and Drug Administration (FDA)-approved Ezvio, an autoinjector that delivers 2mg by intramuscular injection and Narcan nasal spray (2- and 4-mg strengths; 0.1mL/dose) for the emergency treatment of a known or suspected opioid overdose. The present study was conducted to compare the pharmacokinetics of naloxone using the FDA-approved devices (each administered once) and either 1 or 2 administrations using the INND. When naloxone was administered twice using the improvised device, the doses were separated by 2minutes. The highest maximum plasma concentration was achieved using the 4-mg FDA-approved spray. The highest exposures at 5minutes postdose, based on AUC values, were after administration with the autoinjector and the 4-mg FDA-approved spray; at 10, 15, and 20minutes postdose, the latter yielded the greatest exposure. Even after 2 administrations, the INND failed to achieve naloxone plasma levels comparable to the FDA-approved devices at any time. The ease of use and higher plasma concentrations achieved using the 4-mg FDA-approved spray, compared with the INND, should be considered when deciding which naloxone device to use.