PhaseIMetabolismus

Phase I metabolism refers to the initial stage of drug or xenobiotic biotransformation. The primary goal of Phase I reactions is to introduce or expose a polar functional group, such as a hydroxyl, amino, or sulfhydryl group, onto the lipophilic parent compound. This modification generally increases the water solubility of the substance, making it more amenable to excretion or further metabolism in Phase II.

The main types of reactions occurring during Phase I metabolism include oxidation, reduction, and hydrolysis. Oxidative reactions are the most common and are largely catalyzed by the cytochrome P450 (CYP) superfamily of enzymes, located primarily in the liver. Reductive reactions can occur under anaerobic conditions and involve the conversion of functional groups like nitro or azo groups. Hydrolysis involves the cleavage of chemical bonds by the addition of water, often breaking ester or amide linkages.

While Phase I metabolism aims to prepare compounds for excretion, it can also sometimes lead to the formation of reactive intermediates that are more toxic or pharmacologically active than the parent compound. This can have significant implications for drug efficacy, toxicity, and drug-drug interactions. The balance between activating and deactivating pathways within Phase I metabolism is a critical aspect of xenobiotic disposition.