Topic overview

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Phase I reactions—oxidation, reduction, and hydrolysis—introduce or expose functional groups, often preparing a compound for further metabolism. Cytochrome P450 enzymes are major contributors, alongside enzymes such as flavin-monooxygenases, dehydrogenases, esterases, and epoxide hydrolase. Phase I products may be activated, inactivated, or rendered more toxic; they can proceed to Phase II or be excreted directly. Phase II reactions attach endogenous, water-soluble groups through pathways including glucuronidation, sulfation, acetylation, methylation, glutathione conjugation, and amino acid conjugation. Enzyme variation can contribute to differences in clearance and adverse effects. The balance between reaction type, enzyme, and metabolite helps explain the clinical consequences of drug biotransformation.