5.2 : Phase I Oxidative Reactions: Overview

Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular oxygen and the reducing agent NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) to trigger substrate oxidation.

Oxidative reactions can occur at different carbon points in the drug molecule, culminating in the introduction of hydroxyl, carbonyl, or other polar functional groups. For instance, aromatic carbon atom oxidation can transform phenytoin into p-hydroxy phenytoin. Oxidation of aliphatic carbon atoms, as seen in ethanol metabolism, results in alcohols or carboxylic acids. Nitrogen-containing compounds like codeine can undergo various transformations, including N-demethylation, leading to morphine. Sulfur-containing compounds, such as omeprazole, can be converted to sulfoxides or sulfones. Lastly, oxidation of alcohol, carbonyl, and acid functions can lead to aldehydes, ketones, or carboxylic acids.

These reactions are pivotal for drug metabolism, enhancing hydrophilicity and promoting easier elimination. They also facilitate the formation of active metabolites or detoxify harmful compounds. In summary, phase I oxidative biotransformation reactions are indispensable in ensuring the safe and effective use of drugs in the body.