Learning Objective

Understand the general principles of drug biotransformation, the formation of active or inactive metabolites, and the clinical significance of prodrugs and toxic metabolites.

Biotransformation

Biotransformation is the metabolic conversion of drug molecules into more water-soluble metabolites to facilitate excretion.

Inactive metabolites:

• Many drugs are metabolized into compounds with little or no pharmacologic activity.

Example: Diazepam is partially metabolized to inactive metabolites.

Active metabolites:

• Some drugs produce metabolites that retain pharmacologic activity.

Example: Diazepam → nordiazepam (sedative-hypnotic activity).

Prodrugs:

• Inactive compounds that require metabolic activation to become pharmacologically active.

Example: Enalapril → Enalaprilat.

Toxic metabolites:

• Some drugs produce harmful metabolites during metabolism.

Example: Acetaminophen → N-acetyl-p-benzoquinone imine (NAPQI), which can cause hepatotoxicity.

Activity