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Drug Elimination

By Jennifer Le, PharmD, MAS, BCPS-ID, Professor of Clinical Pharmacy and Director of Experiential Education in Los Angeles, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego

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Drug elimination is the removal of drugs from the body.

All drugs are eventually eliminated from the body. They may be eliminated after being chemically altered (metabolized), or they may be eliminated intact. Most drugs, particularly water-soluble drugs and their metabolites, are eliminated largely by the kidneys in urine. Therefore, drug dosing depends largely on kidney function. Some drugs are eliminated by excretion in the bile (a greenish yellow fluid secreted by the liver and stored in the gallbladder).

Elimination in the urine

Several factors, including certain characteristics of the drug, affect the kidneys’ ability to excrete drugs. To be extensively excreted in urine, a drug or metabolite must be water soluble and must not be bound too tightly to proteins in the bloodstream. The acidity of urine, which is affected by diet, drugs, and kidney disorders, can affect the rate at which the kidneys excrete some drugs. In the treatment of poisoning with some drugs, the acidity of the urine is changed by giving antacids (such as sodium bicarbonate) or acidic substances (such as ammonium chloride) orally to speed up the excretion of the drug.

The kidneys’ ability to excrete drugs also depends on

  • Urine flow

  • Blood flow through the kidneys

  • The condition of the kidneys

Kidney function can be impaired by many disorders (especially high blood pressure, diabetes, and recurring kidney infections), by exposure to high levels of toxic chemicals, and by age-related changes. As people age, kidney function slowly declines. For example, the kidneys of an 85-year-old person excrete drugs only about half as efficiently as those of a 35-year-old person.

In people whose kidney function has declined, the “normal” dosage of a drug that is eliminated primarily through the kidneys may be too much and may cause side effects. Therefore, health care practitioners sometimes must adjust the drug dosage based on the amount of decline in the person’s kidney function. People with impaired kidney function require lower drug doses than those with normal kidney function. Health care practitioners have several ways to estimate the decline in kidney function. Sometimes they base an estimate solely on the person’s age. However, they can get a more accurate estimate of kidney function by using the results of tests that measure the level of creatinine (a waste product) in the blood and sometimes also the urine. They use these results to calculate how effectively creatinine is removed from the body (called creatinine clearance—see Kidney Function Tests), which reflects how well the kidneys are functioning.

Elimination in the bile

Some drugs pass through the liver unchanged and are excreted in the bile. Other drugs are converted to metabolites in the liver before they are excreted in the bile. In both scenarios, the bile then enters the digestive tract. From there, drugs are either eliminated in feces or reabsorbed into the bloodstream and thus recycled.

If the liver is not functioning normally, the dosage of a drug that is eliminated primarily by metabolism in the liver may need to be adjusted. However, there are no simple ways to estimate how well the liver will metabolize (and thus eliminate) drugs like there are for kidney function.

Other forms of elimination

Some drugs are excreted in saliva, sweat, breast milk, and even exhaled air. Most are excreted in small amounts. The excretion of drugs in breast milk is significant only because the drug may affect the breastfeeding infant (see Taking Drugs While Breastfeeding). Excretion in exhaled air is the main way that inhaled anesthetics are eliminated.