The body has an elaborate system in which it detoxifies and removes foreign compounds that are ingested or otherwise enter the circulation. Drugs are foreign molecules or compounds that undergo deactivation and elimination from the body. The body performs this function through a process termed metabolism or biotransformation. The goal of drug metabolism is to convert lipophilic compounds (the parent drug in circulation) into a more polar, hydrophilic compound (metabolites) that can be easily dissolved in an aqueous environment such as blood, bile, or urine. Changing the solubility allows the drug and metabolites to be efficiently excreted from the body. Without this chemical biotransformation, most drugs would not be eliminated efficiently and would accumulate in the body, eventually resulting in toxicity.
In general, drug metabolites are less active and less toxic than the parent drug. However, there are exceptions. Morphine, for example, is an active metabolite that is more potent than its parent drug, codeine.
The chemical reactions of metabolism (biotransformation) that result in a change to the drug’s structure are catalyzed by enzymes. These enzymes reside predominately in the liver and small intestine but are widely distributed throughout the body including tissues of the kidneys and lungs as well as in red blood cells, plasma, and saliva. All cells express some level of biotransformation enzymes and thus have some capacity to metabolize drugs. These enzyme-catalyzed reactions can be divided into Phase I and Phase II metabolic reactions.
