M06.01.04 Drug Metabolism

Overview: Drug metabolism, also known as biotransformation, refers to the enzymatic modification of drugs into metabolites, which are often more hydrophilic and easier to excrete from the body. Drug metabolism primarily occurs in the liver but can also take place in other organs such as the intestines, kidneys, and lungs.

Phases of Drug Metabolism:

1. Phase I Reactions: Phase I reactions involve the addition or exposure of functional groups (e.g., hydroxyl, amino, carboxyl) to the drug molecule, usually through oxidation, reduction, or hydrolysis reactions. The primary enzyme system involved in Phase I metabolism is the cytochrome P450 (CYP) enzyme family.
2. Phase II Reactions: Phase II reactions involve the conjugation of the drug or its Phase I metabolites with endogenous molecules such as glucuronic acid, sulfate, or amino acids. This conjugation process increases the water solubility of the drug, facilitating its excretion from the body. Common Phase II enzymes include UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), and glutathione S-transferases (GSTs).

Factors Influencing Drug Metabolism:

• Genetic Variability: Genetic polymorphisms in drug-metabolizing enzymes can lead to interindividual variability in drug metabolism rates and contribute to differences in drug response and toxicity.
• Drug Interactions: Drugs can interact with each other to inhibit or induce drug-metabolizing enzymes, altering the metabolism of co-administered drugs and potentially leading to therapeutic failure or toxicity.
• Disease States: Physiological conditions such as liver disease, renal impairment, and metabolic disorders can affect drug metabolism by altering enzyme activity and expression levels.
• Age and Sex: Drug metabolism may vary with age and sex due to differences in enzyme expression, hormonal influences, and organ function.
• Environmental Factors: Environmental factors such as diet, smoking, alcohol consumption, and exposure to environmental toxins can influence drug metabolism by affecting enzyme activity and expression.

Clinical Implications:

• Understanding drug metabolism is essential for predicting the pharmacokinetics and pharmacodynamics of drugs, optimizing dosing regimens, and minimizing the risk of adverse drug reactions.
• Knowledge of metabolic pathways can help clinicians identify potential drug interactions and select appropriate therapeutic agents for patients with altered metabolic capacity.
• Pharmacogenetic testing can assist in personalized medicine by identifying individuals with genetic variations that affect drug metabolism, allowing for tailored treatment strategies.

In summary, drug metabolism plays a critical role in determining the fate of drugs in the body and their pharmacological effects. Factors such as genetic variability, drug interactions, and disease states can influence drug metabolism, highlighting the importance of considering individual patient factors in clinical practice.