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Drug Metabolism


Jennifer Le

, PharmD, MAS, BCPS-ID, FIDSA, FCCP, FCSHP, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego

Last full review/revision Oct 2020| Content last modified Oct 2020

Drug metabolism is the chemical alteration of a drug by the body.

(See also Introduction to Administration and Kinetics of Drugs.)

Some drugs are chemically altered by the body (metabolized). The substances that result from metabolism (metabolites) may be inactive, or they may be similar to or different from the original drug in therapeutic activity or toxicity. Some drugs, called prodrugs, are administered in an inactive form, which is metabolized into an active form. The resulting active metabolites produce the desired therapeutic effects. Metabolites may be metabolized further instead of being excreted from the body. The subsequent metabolites are then excreted. Excretion involves elimination of the drug from the body, for example, in the urine or bile.

Most drugs must pass through the liver, which is the primary site for drug metabolism. Once in the liver, enzymes convert prodrugs to active metabolites or convert active drugs to inactive forms. The liver’s primary mechanism for metabolizing drugs is via a specific group of cytochrome P-450 enzymes. The level of these cytochrome P-450 enzymes controls the rate at which many drugs are metabolized. The capacity of the enzymes to metabolize is limited, so they can become overloaded when blood levels of a drug are high (see Genetic Makeup and Response to Drugs).

Many substances (such as drugs and foods) affect the cytochrome P-450 enzymes. If these substances decrease the ability of the enzymes to break down a drug, then that drug's effects (including side effects) are increased. If the substances increase the ability of the enzymes to break down a drug, then that drug's effects are decreased.

Because metabolic enzyme systems are only partially developed at birth, newborns have difficulty metabolizing certain drugs. As people age, enzymatic activity decreases, so that older people, like newborns, cannot metabolize drugs as well as younger adults and children do (see Aging and Drugs). Consequently, newborns and older people often need smaller doses per pound of body weight than do young or middle-aged adults.

Genetic variations in how certain drugs (for example, statins) are transported into and out of the liver may increase a person's risk of drug side effects or drug-related liver injury.

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