@article{ref1,
title="Fighting fire with fire: development of intranasal nalmefene to treat synthetic opioid overdose",
journal="Journal of pharmacology and experimental therapeutics",
year="2019",
author="Krieter, Philip and Gyaw, Shwe and Crystal, Roger and Skolnick, Phil",
volume="ePub",
number="ePub",
pages="ePub-ePub",
abstract="The dramatic rise in overdose deaths linked to synthetic opioids (e.g., fentanyl, carfentanil) may require more potent, longer duration opiate antagonists than naloxone. Both the high affinity of nalmefene at μ opiate receptors and its long half-life led us to examine the feasibility of developing an intranasal (IN) formulation as a rescue medication that could be especially useful in treating synthetic opioid overdose. In this study, the pharmacokinetic properties of IN nalmefene were compared with an intramuscular (IM) injection in a cohort of healthy volunteers. Nalmefene was absorbed slowly following IN administration, with a median T<sub>max</sub> of 2 h. Addition of the absorption enhancer dodecyl maltoside (Intravail®) reduced T<sub>max</sub> to 0.25 h and increased C <sub>max</sub> by ~2.2-fold. The pharmacokinetic properties of IN nalmefene (3 mg) formulated with dodecyl maltose has characteristics consistent with an effective rescue medication: its onset of action is comparable to an IM injection of nalmefene (1.5 mg) previously approved to treat opioid overdose. Furthermore, the C<sub>max</sub> following IN administration is ~3-fold higher than following IM dosing, comparable to previously reported plasma concentrations of nalmefene observed 5 min. following a 1 mg IV dose. The high affinity, very rapid onset, and long half-life (>7 h) of IN nalmefene present distinct advantages as a rescue medication, particularly against longer-lived synthetic opioids.<br><br>The American Society for Pharmacology and Experimental Therapeutics.<p /> <p>Language: en</p>",
language="en",
issn="0022-3565",
doi="10.1124/jpet.118.256115",
url="http://dx.doi.org/10.1124/jpet.118.256115"
}