In the process of converting a drug to a metabolite, the pharmacological activity of the drug may be changed. Metabolites can be broadly classified as either inactive or active metabolites.

  • Inactive metabolites of drugs are devoid of pharmacological activity that was characteristic of the drug or toxicant. This metabolic change may be considered an inactivation or detoxification. 
  • Active metabolites of drugs have pharmacological activity, which can either be similar to the desired pharmacological activity or a new activity that is absent from the parent drug.

In the case that the metabolite has the desired pharmacological activity although the parent is inactive, the metabolism is called bioactivation. The parent compound devoid of pharmacological activity before metabolism is called a prodrug.
  • For example, the prodrug enalapril (Vasotec) is hydrolyzed to enalaprilat, a potent antihypertensive.

Bioactivation of a drug can also result in a toxic metabolite. The parent activated is called a protoxicant.
  • Halothane (Fluothane) is a general anesthetic that is oxidized to a reactive metabolite that is associated with hepatotoxicity.
  • Acetaminophen (Tylenol) can be oxidized into a reactive metabolite, N-acetyl-p-benzoquinoneimine (NAPQI), that can lead to hepatotoxicity.

Drug metabolism is performed by a large number of different enzymes and even by some nonenzymatic processes. The liver is the organ with the highest concentration of drug-metabolizing enzymes because of its localization between the gastrointestinal (GI) tract, where the body has the highest exposure to foreign substances, and the systemic circulation. The enzymes involved in drug metabolism can be classified by several different categories. The enzymes can either be localized in the cytosol (cytosolic) or the endoplasmic reticulum (ER) membrane (microsomal) portion of the cell. A general classification of enzymatic processes based on the type of reactions involved includes phase I and phase II.

  • Phase I metabolism is characterized as a functionalization reaction. Phase I reactions add or reveal a polar functional group on a substrate by oxidation, reduction, or hydrolysis.
  • Phase II reactions are commonly called conjugation reactions because they use a functional group on the xenobiotic (either from phase I metabolism or part of the xenobiotic itself) to add or conjugate a biomolecule that usually increases the polarity of the xenobiotic and facilitates elimination from the body. These conjugation reactions require an enzyme generally termed as transferase that transfers a high-energy molecule called the cofactor or cosubstrate to the xenobiotic.