5.1 : Drug Biotransformation: Overview

Biotransformation, also known as drug metabolism, is a vital physiological process that chemically alters drugs, facilitating their elimination from the body and terminating their action. This process involves two main phases: phase I and phase II reactions. Phase I reactions, including oxidation, reduction, and hydrolysis, introduce or unmask polar functional groups on the drug molecule, thereby increasing its water solubility. By enhancing water solubility, the drug becomes more hydrophilic and is less likely to be reabsorbed in the lipophilic environment of renal tubules during excretion. This modification ensures that the drug and its metabolites are excreted efficiently via urine or bile, as hydrophilic substances are more readily eliminated by the kidneys. Phase II or conjugation reactions further enhance water solubility by attaching small polar molecules to the drug or its phase I metabolites. Examples include glucuronidation, sulfation, acetylation, methylation, and glutathione conjugation.

The liver, laden with drug-metabolizing enzymes, is the primary site for drug metabolism. However, other organs like the lungs, kidneys, intestines, and placenta also contribute. The enzymes responsible for drug metabolism fall into two categories: microsomal and non-microsomal. Microsomal enzymes in the endoplasmic reticulum catalyze most drug biotransformation reactions, while non-microsomal enzymes in the cytoplasm and mitochondria play a subsidiary role.

Drug metabolism detoxifies xenobiotics, activates prodrugs, and inactivates active drugs, preventing drug accumulation and reducing toxicity risk. However, it can also form reactive metabolites, potentially causing adverse effects. In essence, understanding biotransformation is crucial for predicting drug interactions, optimizing drug therapy, and ensuring patient safety.