ArticlePloS one2020
Higher naloxone dosing in a quantitative systems pharmacology model that predicts naloxone-fentanyl competition at the opioid mu receptor level.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Does Kappa Agonism Improve Reversal of 'Tranq-Dope' Overdose? Evidence from a Rodent Model.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Naloxone Administration in Relation to Fentanyl, Xylazine, CNS Depressants, and Stimulants Exposure After Suspected Opioid Overdose: A Pilot Study.Academic emergency medicine : official journal of the Society for Academic Emergency Medicine · 2026Observational
- Naloxone reversal of fentanyl-induced respiratory depression versus naloxone-induced precipitated withdrawal: anFrontiers in pharmacology · 2026Article
- Combining the alpha-2 adrenergic agonist clonidine with naloxone rescues fentanyl-induced physiologic dysfunction and increases survival.bioRxiv : the preprint server for biology · 2025Article
- Naloxone dosing in the era of synthetic opioids: Applying the Goldilocks principle.Addiction (Abingdon, England) · 2025Review
- Ultrafast terahertz-induced torque disruption of fentanyl's μ-opioid receptor binding for precision overdose reversal.Journal of molecular modeling · 2025Article
- Treating Opioid Use Disorder and Opioid Withdrawal in the Context of Fentanyl.Annual review of clinical psychology · 2025Review
- An implantable system for opioid safety.Device · 2024Article
- Mechanistic pharmacokinetic-pharmacodynamic modeling and simulations of naloxone auto-injector 10 mg reversal of opioid-induced respiratory depression.CPT: pharmacometrics & systems pharmacology · 2024Article
- Synthetic opioids have disrupted conventional wisdom for treating opioid overdose.Drug and alcohol dependence reports · 2024Article
- Clinical Pharmacokinetics and Pharmacodynamics of Naloxone.Clinical pharmacokinetics · 2024Review
- Fact vs. fiction: naloxone in the treatment of opioid-induced respiratory depression in the current era of synthetic opioids.Frontiers in public health · 2024Review
- Are carfentanil and acrylfentanyl naloxone resistant?Frontiers in psychiatry · 2024Article
- Pharmacokinetic Properties of an FDA-approved Intranasal Nalmefene Formulation for the Treatment of Opioid Overdose.Clinical pharmacology in drug development · 2024Article
- Fentanyl activates opposing opioid and non-opioid receptor systems that control breathing.Frontiers in pharmacology · 2024Article
- Heroin- and Fentanyl-Induced Respiratory Depression in a Rat Plethysmography Model: Potency, Tolerance, and Sex Differences.The Journal of pharmacology and experimental therapeutics · 2023Article
- Mechanisms of Neurorespiratory Toxicity Induced by Fentanyl Analogs-Lessons from Animal Studies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Amphetamines modulate fentanyl-depressed respiration in a bidirectional manner.Drug and alcohol dependence · 2023Article
- Pharmacological Profiling of Antifentanyl Monoclonal Antibodies in Combination with Naloxone in Pre- and Postexposure Models of Fentanyl Toxicity.The Journal of pharmacology and experimental therapeutics · 2022Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rapid resuscitation of an opioid overdose with naloxone, an opioid antagonist, is critical. We developed an opioid receptor quantitative systems pharmacology (QSP) model for evaluation of naloxone dosing. In this model we examined three opioid exposure levels that have been reported in the literature (25 ng/ml, 50 ng/ml, and 75 ng/ml of fentanyl). The model predicted naloxone-fentanyl interaction at the mu opioid receptor over a range of three naloxone doses. For a 2 mg intramuscular (IM) dose of naloxone at lower fentanyl exposure levels (25 ng/ml and 50 ng/ml), the time to decreasing mu receptor occupancy by fentanyl to 50% was 3 and 10 minutes, respectively. However, at a higher fentanyl exposure level (75 ng/ml), a dose of 2 mg IM of the naloxone failed to reduce mu receptor occupancy by fentanyl to 50%. In contrast, naloxone doses of 5 mg and 10 mg IM reduced mu receptor occupancy by fentanyl to 50% in 5.5 and 4 minutes respectively. These results suggest that the current doses of naloxone (2 mg IM or 4 mg intranasal (IN)) may be inadequate for rapid reversal of toxicity due to fentanyl exposure and that increasing the dose of naloxone is likely to improve outcomes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.