From the Guidelines
Phase 1 Metabolic Reactions
Phase 1 of metabolism encompasses a series of biochemical reactions that modify the chemical structure of xenobiotics, including drugs, to increase their water solubility. This phase includes various reactions such as:
- Hydroxylation, which is catalyzed by cytochrome P450 enzymes 1 and is involved in the metabolism of medications like phenytoin and warfarin.
- Acetylation, which plays a crucial role in the biotransformation of certain drugs, such as isoniazid.
- Sulphonation, which is another important reaction in the metabolism of drugs.
- Isomerization, which is also involved in the biotransformation of certain drugs. These reactions are crucial in the metabolism of many drugs, and understanding them is essential in predicting and managing drug-drug interactions 1. The cytochrome P450 enzymes, particularly CYP3A4, play a significant role in the phase I metabolism of many drugs 1.
From the FDA Drug Label
Isoniazid is metabolized primarily by acetylation and dehydrazination. The answer to the question is that acetylation is an example of a Phase 1 metabolic reaction.
- Other examples of Phase 1 metabolic reactions mentioned in the question, such as sulfonation, isomerization, and hydroxylation, are not mentioned in the drug label as metabolic reactions for isoniazid. 2
From the Research
Phase 1 Metabolic Reactions
Phase 1 metabolic reactions involve the conversion of a lipophilic xenobiotic into a more hydrophilic compound, typically through oxidation, reduction, or hydrolysis reactions. Examples of Phase 1 metabolic reactions include:
- Acetylation: the introduction of an acetyl group into a xenobiotic compound 3
- Sulfonation: the introduction of a sulfonate group into a xenobiotic compound 3
- Isomerization: the conversion of a xenobiotic compound into its isomeric form 4
- Hydroxylation: the introduction of a hydroxyl group into a xenobiotic compound, typically catalyzed by cytochrome P450 enzymes 5, 6, 7
Enzymes Involved in Phase 1 Metabolic Reactions
Several enzymes are involved in Phase 1 metabolic reactions, including:
- Cytochrome P450 enzymes: a superfamily of enzymes that play a major role in the biotransformation of xenobiotics 5, 6, 7
- Flavin-containing monooxygenases: enzymes that catalyze the oxidation of xenobiotics 7
- Alcohol dehydrogenase: an enzyme that catalyzes the oxidation of alcohols to aldehydes or ketones 3
- Ester and amide hydrolases: enzymes that catalyze the hydrolysis of esters and amides 3