Phase I Metabolism
Definition
Functionalisation reactions (oxidation, reduction, hydrolysis) that introduce or expose a polar group on the drug molecule, mostly catalysed by cytochrome P450 isoenzymes in the hepatic endoplasmic reticulum. Produces metabolites that may be active, inactive or more toxic than the parent.
- Reaction types
- Oxidation, reduction, hydrolysis
- Main enzyme family
- Cytochrome P450 isoenzymes
- Location
- Hepatic endoplasmic reticulum
- Outcome
- Metabolite may be active, inactive or more toxic
Common questions
Can a Phase I metabolite be more toxic than the original drug?+
Yes, functionalisation sometimes produces a reactive or more pharmacologically potent metabolite, which is why some drugs are more dangerous through their breakdown products than through the parent compound itself.
Does Phase I metabolism always have to happen before Phase II?+
No. Some compounds already carry a polar group suitable for direct conjugation and can undergo Phase II metabolism without first passing through Phase I functionalisation.
Related terms
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- Phase II Metabolism
- Conjugation reactions (glucuronidation, sulphation, glutathione conjugation, acetylation, methylation, glycine conjugation) that attach a polar endogenous group to the drug or its Phase...
- Post-Mortem Redistribution (PMR)
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- Therapeutic, Toxic and Lethal Ranges
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- Volume of Distribution (Vd)
- The apparent volume in which a drug is distributed in the body, calculated as dose divided by plasma concentration at time zero....