Bioactivation

Overview of bioactivation in pharmacology and toxicology

Bioactivation is a biochemical process in which a substance is metabolically converted into a more active or toxic form. This process is significant in the fields of pharmacology and toxicology, as it can influence the efficacy and safety of drugs and other chemicals.

Overview

Bioactivation typically involves the conversion of a prodrug into its active form or the transformation of a chemical into a reactive metabolite. This process is primarily mediated by enzymes, particularly those in the cytochrome P450 family, which are abundant in the liver.

Mechanisms

Bioactivation can occur through various mechanisms, including:

• Oxidation: The addition of oxygen or the removal of hydrogen, often catalyzed by cytochrome P450 enzymes.
• Reduction: The gain of electrons or hydrogen, which can also be enzyme-mediated.
• Hydrolysis: The cleavage of chemical bonds by the addition of water, often involving esterases or amidases.

Examples

• Prodrugs: Many medications are administered as prodrugs, which are inactive until bioactivated. For example, codeine is bioactivated to morphine by the enzyme CYP2D6.
• Toxic Metabolites: Some substances are bioactivated to toxic metabolites. For instance, acetaminophen is bioactivated to a reactive metabolite that can cause liver damage in high doses.

Clinical Implications

Understanding bioactivation is crucial for drug development and safety assessment. It helps in predicting drug interactions, adverse effects, and individual variability in drug response.

Drug Development

In drug development, identifying the bioactivation pathways can aid in designing safer and more effective drugs. Researchers aim to optimize the balance between therapeutic efficacy and toxicity.

Toxicology

In toxicology, bioactivation is a key factor in assessing the potential risks of chemicals. It is important to identify which metabolites are formed and their effects on the body.

Also see

• Metabolism (pharmacology)
• Cytochrome P450
• Prodrug
• Toxicology
• Pharmacokinetics