Phase II Metabolism
Definition
Conjugation reactions (glucuronidation, sulphation, glutathione conjugation, acetylation, methylation, glycine conjugation) that attach a polar endogenous group to the drug or its Phase I metabolite, producing a water-soluble conjugate suitable for renal or biliary excretion.
- Reaction types
- Glucuronidation, sulphation, acetylation, methylation
- Purpose
- Attach a polar group to increase water solubility
- Excretion route
- Renal or biliary
- Substrate
- Parent drug or its Phase I metabolite
Common questions
Why is Phase II conjugation necessary after Phase I oxidation?+
Phase I products are often only mildly more polar than the parent drug and can still be poorly excreted, so Phase II conjugation attaches a strongly polar endogenous group that makes the compound water-soluble enough for efficient renal or biliary clearance.
Can Phase II metabolism occur on a drug that never underwent Phase I metabolism?+
Yes, if the drug already has a chemical group such as a hydroxyl or amine that conjugation enzymes can act on directly, it can be conjugated without any preceding Phase I transformation.
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