Naloxone reversal of fentanyl-induced respiratory depression versus naloxone-induced precipitated withdrawal: an in silico utility model

Background

Naloxone reverses opioid-induced respiratory depression (RD) but may precipitate withdrawal in opioid-dependent individuals. Although both have been studied separately, their concentration-response relationships have not been described within a single model. We developed a mechanistic pharmacokinetic/pharmacodynamic simulation model combining an established model of naloxone-induced reversal of fentanyl-induced RD with a novel mechanistic model of precipitated withdrawal based on normalized μ-opioid receptor activation.