eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2026-08-18 23 3 59574 article Deepa Sreekanth 1 Sreekanth Sudhan Kaithavallapil 2 Aiswarya Kundukattil Narayanan 1 Twinkle Nerkadi Unniyalungal 1 Divya Gupta Palotil Kunhunni 1 Department of Pharmaceutics, Nehru College of Pharmacy, Thrissur, India Department of Pharmaceutics, Indira Gandhi Institute of Pharmaceutical Sciences, Perumbavoor ,India Cytochrome P450 (CYP450) enzymes are the principal catalysts of Phase I drug metabolism and play a central role in determining drug disposition, therapeutic efficacy, and toxicity. These heme-containing monooxygenases metabolise numerous endogenous compounds and xenobiotics, including most clinically used drugs. Alterations in CYP450 activity through enzyme inhibition or induction are major mechanisms underlying clinically significant drug–drug interactions (DDIs), which can lead to therapeutic failure or adverse drug reactions. This mechanistic review provides a comprehensive overview of the structural organisation, catalytic cycle, and regulatory mechanisms governing CYP450-mediated drug metabolism. Particular emphasis is placed on the major human CYP isoenzymes—CYP3A4, CYP2D6, CYP2C9, CYP2C19, and CYP1A2—with respect to their substrate specificity, metabolic functions, and clinical relevance. The review discusses the molecular basis of competitive, non-competitive, and mechanism-based inhibition, as well as enzyme induction, highlighting their effects on drug clearance, bioavailability, and systemic exposure. In addition, the influence of physiological, pathological, genetic, epigenetic, and environmental factors on CYP450 activity is examined to explain interindividual variability in drug response. Emerging technologies, including pharmacogenomics, proteomics, metabolomics, physiologically based pharmacokinetic (PBPK) modelling, and artificial intelligence (AI)-based predictive approaches, are also discussed for their potential to improve the prediction of CYP450-mediated metabolism and DDIs.  By integrating structural, biochemical, pharmacological, clinical, and technological perspectives, this review highlights the importance of CYP450 enzymes in optimising drug therapy, minimising adverse drug reactions, and advancing precision medicine. https://www.biotech-asia.org/vol23no3/cytochrome-p450-enzymes-and-drug-interactions-a-mechanistic-review/ Cytochrome P-450 Enzymes; Drug Interactions; Drug Metabolism; Enzyme Induction; Inhibition; Pharmacokinetics