Richard Tecwyn Williams (1909–1979)
What happens to a drug after it has entered your blood and acted for some finite period? Is it doomed to sail eternally around your body like the legendary ship The Flying Dutchman? Drug metabolism prevents our bodies from becoming junkyards for all the drugs we have ever taken. The drug-clearing process of metabolism (or biotransformation) chemically converts drugs into products called metabolites that can be more readily excreted from the body by the kidney, the major organ of drug elimination. These chemical changes require the presence of biological catalysts called enzymes, primarily located in the liver, which permit animals to eliminate foreign toxic chemicals. In his classic 1947 work, Detoxification Mechanisms, R. T. Williams defined these reactions and laid the foundation for the study of drug metabolism.
The speed at which drugs are metabolized determines the intensity and length of their effects. If the rate of metabolism is slowed by reducing the activity of these drug-metabolizing enzymes, the drug will act with greater force for a longer than normal period, increasing the risk of toxicity. Conversely, speeding up the rate of metabolism (enzyme induction) by smoking cigarettes, for example, can reduce the intensity and effectiveness of the drug and shorten the time it continues to act.
Metabolism explains, in part, why some individuals or groups of individuals are highly sensitive to drugs, while others are more resistant. Some differences can be attributed to other drugs taken concurrently that have the potential to stimulate or inhibit the activity of drug-metabolizing enzymes. Other factors that modify the rate of metabolism include the age of the patient (low enzyme activity in infants, young children, and the elderly) and genetic factors. Members of certain Asian groups (Chinese, Japanese, Koreans) are more sensitive to the effects of alcohol than Caucasians—a difference attributed to a deficiency of the enzyme aldehyde dehydrogenase.
In the past, metabolism was thought to transform chemical compounds into metabolites that had less biological activity than their parent drug. Usually this is true, but not always. Levodopa is inactive, but when it enters the brain it is metabolized to dopamine, which is effective for the treatment of Parkinson’s disease.
SEE ALSO Chloramphenicol (1949), Succinylcholine (1951), Isoniazid (1951), Malathion (1951).
Certain ethnic groups, or individuals within a given ethnic group, may differ from the general population in their ability to metabolize drugs. New drugs are increasingly being tailored to treat those few individuals whose unusual response to them is based on a genetically associated, atypical drug metabolism.