The oxidoreductase hemoprotein CYP3A4 of the cytochrome P450 family of enzymes is involved in metabolism of a wide range of xenobiotics in the body. This includes numerous antidepressants, antifungals, antipsychotics, opioids, and antibiotics. The enzyme is capable of binding to more than one substrate at a time and activates or deactivates drugs by chemical mechanisms such as hydroxylation, dehydrogenation, dealkylation and oxidation. Fentanyl is one of the most potent schedules – II drugs classified by the U.S. Drug Enforcement Administration. The drug in itself is 50-100 times more potent than morphine with a lethal dose of 2.0-3.0 mg and also has analogues such as carfentanil which can be even more potent than the parent compound. In the present study docking of fentanyl to CYP3A4 was attempted using Auto Dock tools and PyMOL to analyse the binding of fentanyl and its deactivation to norfentanyl by the enzyme. The enzyme deactivates a ligand containing a Cα and a nitrogen heteroatom by oxidative dealkylation which can be hypothesized to follow electron-proton transfer. Molecular docking and analysis by AutoDock Vina and PyMOL respectively showed a flexible binding of fentanyl in the active site of CYP3A4 which indicates that the ligand can serve as a substrate for the enzyme and can be dealkylated to produce norfentanyl. Norfentanyl is then typically excreted through urine within 3-4 days and around 0.4-6% drug is excreted out as fentanyl while some percentage of drug may be secreted out as other smaller metabolites.

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