Research Progress of Fentanyl

OBJECTIVES: Fentanyl, a potent μ receptor agonist, is a cornerstone of perioperative and cancer pain management due to its high efficiency and multidosage characteristics. Despite its efficacy, the risks of respiratory depression and abuse present significant global public health challenges. The development of novel drug delivery systems expands their utility but intensifies the need to balance clinical benefits with safety. This review synthesizes recent evidence on fentanyl pharmacology and clinical use, with a focus on multimodal administration strategies, dose adjustment for special populations, and the impact of antiabuse technologies and regulatory policies. METHODS: From the establishment of the database to September 2025, researchers conducted a systematic literature search in PubMed, Embase, and CNKI databases. The search terms included "fentanyl," "analgesia," "pharmacokinetics," "respiratory depression," and "abuse prevention." High-quality randomized controlled trials, meta-analysis, literature review, and the latest clinical guidelines were included. RESULTS: Analysis confirmed that fentanyl's unique pharmacokinetics and its newly discovered multivalent binding mode to the μ-receptor underpin its rapid onset and potent analgesia. Quantitative comparisons showed intravenous administration excels in rapid-onset pain relief, while mucosal routes provide superior sustained drug exposure. Critically, dose reduction is essential for elderly patients and those with hepatic impairment. DISCUSSION: The effective use of fentanyl requires an integrated strategy combining pharmacological knowledge, individual patient factors, and a robust regulatory framework. The integration of antiabuse formulation and stringent regulatory measures is vital for mitigating misuce risks while ensuring medical accessbibility.The clinical decision-making pathway proposed herein aids in optimizing analgesia and minimizing adverse outcomes. Future research should prioritize developing evidence-based guidelines for the Chinese population and exploring genomic predictors for personalized pain management.