Is Fentanyl Rebound an Intrinsic Feature of Naloxone Reversal?

ABSTRACT: Background/Objectives: The drug development response to the unique pharmacology of fentanyl, which drives the current opioid epidemic, has primarily focused on increasing naloxone doses and employing longer-acting antidotes. While having lower withdrawal liability, the commonly perceived disadvantage of naloxone is its reduced effectiveness against re-narcotization or "fentanyl rebound," due to a significant mismatch between its half-life (t_1/2) and that of fentanyl. Methods: We conducted a pharmacokinetic profile (PK) crossover study in fentanyl-sedated dogs to assess naloxone (NX) and its lipophilic prodrug (NX90) with regard to fentanyl PK and re-narcotization risk. Results: Our findings showed that naloxone redistributed fentanyl into the plasma, with co

SUBMITTER: Voronkov M 

PROVIDER: S-EPMC12654983 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature