TY  - JOUR
PY  - 2019//
TI  - Fighting fire with fire: development of intranasal nalmefene to treat synthetic opioid overdose
JO  - Journal of pharmacology and experimental therapeutics
A1  - Krieter, Philip
A1  - Gyaw, Shwe
A1  - Crystal, Roger
A1  - Skolnick, Phil
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - 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>
LA  - en
SN  - 0022-3565
UR  - http://dx.doi.org/10.1124/jpet.118.256115
ID  - ref1
ER  -