Active metabolites

1. Active Metabolites

Active metabolites are biologically active forms of drugs that result from the metabolic conversion of the parent compound. These metabolites can contribute significantly to the pharmacological or toxicological effects of the drug. Understanding active metabolites is crucial in pharmacology and medicine, as they can influence the efficacy and safety of therapeutic agents.

Metabolism Overview

Metabolism is the process by which the body breaks down and converts drugs into more water-soluble compounds for excretion. This process primarily occurs in the liver and involves two phases:

• Phase I Metabolism: This phase involves chemical modifications such as oxidation, reduction, or hydrolysis. Enzymes like cytochrome P450 play a significant role in this phase.
• Phase II Metabolism: This phase involves conjugation reactions where the drug or its Phase I metabolite is linked with another substance (e.g., glucuronic acid, sulfate) to increase solubility.

Active metabolites can be formed during either phase, but they are most commonly associated with Phase I reactions.

Examples of Active Metabolites

Several drugs are known to have active metabolites that contribute to their therapeutic effects:

• Codeine: Metabolized to morphine, which is responsible for most of its analgesic effects.
• Diazepam: Metabolized to desmethyldiazepam, which has a long half-life and contributes to its sedative effects.
• Clopidogrel: Requires metabolic activation to produce an active metabolite that inhibits platelet aggregation.

Clinical Implications

The presence of active metabolites can have several clinical implications:

• Efficacy: Active metabolites can enhance or prolong the therapeutic effects of a drug.
• Toxicity: Some active metabolites may be toxic, leading to adverse effects. For example, acetaminophen is metabolized to a toxic metabolite that can cause liver damage in overdose situations.
• Drug Interactions: Metabolism can be affected by other drugs, leading to increased or decreased levels of active metabolites.

Pharmacogenomics

Genetic variations can affect the metabolism of drugs, leading to differences in the formation of active metabolites. This is an important consideration in pharmacogenomics, where genetic testing can guide drug therapy to optimize efficacy and minimize adverse effects.

Also see

• Metabolism
• Pharmacokinetics
• Prodrug
• Cytochrome P450
• Pharmacogenomics