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Updated: Mar 22, 2026

Author Spotlight: An Efficient Methodology to Confidently Differentiate and Characterize Fentanyl Analogs
Published on: November 8, 2024
First ADME profile of fentanyl (437-38-7) - synthetic opioid driving overdose epidemics: Comprehensive in silico
Łukasz Niżnik1, Oktawia Fijałkowska2, Varun Ahuja3
1Department of Regulatory and Forensic Toxicology, Institute of Medical Expertises, Łódź, ul. Aleksandrowska 67/93, 91-205, Łódź, Poland.
Abstract:
Fentanyl is a synthetic opioid used as an analgesic and anesthetic agent. In recent years, it has been referred to as the "zombie drug" and is estimated to be responsible for the majority of opioid overdose deaths in North America. This study provides a comprehensive characterization of fentanyl's ADME properties, generated using multiple in silico tools (ADMETlab 3.0, ADMET Predictor 12.0, ACD/Percepta, BioTransformer 3.0, Deep-PK, DruMAP 2.0, pkCSM, SwissADME, and XenoSite). The compound demonstrated high gastrointestinal absorption (approaching 100%), high lipophilicity (with consistent LogP values of 3.75 - 4.14), low to moderate solubility (-6.26 to -3.56), and Caco-2 permeability of1.95 × 10-5 cm/s. Furthermore, the results indicate strong plasma protein binding (86.2-92.18%) and a volume of distribution ranging from 1.01 to 14.62 L/kg. Metabolic profiling identified five metabolites (M1-M5), and metabolic hotspot visualization was performed. Total clearance of the compound ranged from 0.996 to 8.598 mL/min/kg, indicating low to moderate elimination, with a short half-life (T1/2) ranging from 0.664 h to less than 3 h, and OCT2-mediated renal excretion is expected. Through the use of multiple in silico platforms, a comprehensive ADME profile of fentanyl was established, providing valuable insights for clinical toxicology and forensic investigations of illicit use.
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