Section 2. Drugs

Chapter 11. Drug Administration and Kinetics

Topics: Introduction | Drug Administration | Drug Absorption | Drug Distribution | Drug Metabolism | Drug Elimination

Drug Elimination

Drug elimination is the removal of drugs from the body.

All drugs are eliminated from the body in a chemically altered (metabolized) form or by excretion. Most drugs, particularly water-soluble drugs and their metabolites, are eliminated largely by the kidneys in 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, and 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 decreases. The kidney of an 85-year-old person excretes drugs only about half as efficiently as that of a 35-year-old.

Doctors may adjust the dosage of a drug that is eliminated primarily through the kidneys. The normal age-related decrease in kidney function can help doctors determine an appropriate dosage based solely on a person's age. However, appropriate dosage can be determined more accurately by determining how well the kidneys are functioning: A blood test can be performed to measure the level of creatinine (a waste product) in the blood, or a urine test may be performed so that the amount of creatinine in urine collected for 12 to 24 hours relative to the level of creatinine in the blood--called creatinine clearance--can be estimated.

Some drugs pass through the liver and are excreted unchanged in the bile. The bile then enters the digestive tract. From there, drugs are eliminated in feces or reabsorbed into the bloodstream and thus recycled. Other drugs are converted to metabolites that are excreted in the bile. The metabolites may be excreted in the feces or converted back to the drug, which is then reabsorbed into the bloodstream and recycled.

If the liver is not functioning normally, doctors may adjust the dosage of a drug that is eliminated primarily by metabolism in the liver. However, there are no simple ways to assess liver function quantitatively for drug metabolism comparable to those for kidney function.

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. Excretion in exhaled air is the main way that inhaled anesthetics are eliminated.