Drug metabolism

Drug metabolism, also known as xenobiotic metabolism or biotransformation, is the complex biochemical process by which a living organism chemically modifies pharmaceutical substances, primarily through specialized enzymatic systems in the liver (StatPearls, 2023). This process is categorized into Phase I reactions, which introduce functional groups via oxidation, reduction, or hydrolysis, and Phase II reactions, which involve the conjugation of the drug to polar molecules to increase water solubility (NIH, 2021). The primary biological role of drug metabolism is the detoxification and elimination of foreign compounds from the body, though it is also essential for the activation of prodrugs into their pharmacologically active forms (PubMed, 2022). Significant variability in drug metabolism arises from genetic polymorphisms, age, sex, and environmental factors, which can lead to adverse drug reactions or therapeutic failure (FDA, 2020). The Cytochrome P450 (CYP) enzyme superfamily is the most critical component of this system, responsible for the metabolism of the majority of clinically used drugs (UniProt, 2024). Consequently, drug metabolism is a major consideration in drug development and clinical practice due to its central role in drug-drug interactions and toxicity (Wikipedia, 2024).

Other names

Xenobiotic metabolismBiotransformationPhase I and Phase II metabolismDrug clearance pathwayPharmacometabolomics

Modulation of enzymatic activity (induction or inhibition) of Cytochrome P450 (CYP) enzymes, UDP-glucuronosyltransferases (UGTs), and drug transporters (e.g., P-glycoprotein) to alter the rate of chemical modification and excretion of compounds.