Drugs are eliminated from the body
either unchanged as the parent drug or
as metabolites (a changed form of the
Organs that excrete drugs eliminate
polar compounds (water soluble) more
readily than components with high lipid
(fat) solubility. The exception to this
premise is the lungs.
Lipid soluble drugs are not readily
eliminated until they are metabolized to
more polar compounds.
Possible sources of excretion include:
The kidney is the most important organ
involved in the elimination of drugs and
Substances excreted in the feces
usually involve orally ingested
unabsorbed drugs or metabolites excreted
in the bile that are not reabsorbed from
the intestinal tract.
Excretion of drugs in milk is relevant
because excreted drugs can produce drug
toxicity in the nursing infant.
Pulmonary excretion (through breathing)
is important as it pertains to the
elimination of anesthetic gases and
vapors, as well as alcohol.
Excretion through the kidneys
The kidneys are a pair of bean-shaped
organs, each a little smaller than the
fist and weighing about 0.25 pounds.
They lie on the back of the abdominal
cavity at the level of the lower ribs.
They act as a pressure filter. On its
way through the kidneys the blood is
filtered. The liquid or "primary urine"
consists of a considerable amount of the
blood's water, together with all
substances dissolved in this water
(including drugs). The kidneys reabsorb
most of the water and some of the
dissolved substances. Components that
are fat-soluble tend to diffuse back
into the bloodstream.
The kidneys perform two major
- They excrete most of the
end-products of body metabolism
(including drugs); They closely
regulate the levels of most of the
substances found in body fluids.
- Substances that must be excreted
include the end-products of body
metabolism, as well as sodium,
potassium, and chloride, which
frequently accumulate in the body in
excess quantities. The kidneys must
also be capable of conserving water,
sugar, and the necessary quantities of
sodium, potassium and chloride.
Since drugs are small particles
dissolved in the blood, they too are
usually filtered into the kidneys and
then reabsorbed back into the
Water is reabsorbed from the kidney
into the bloodstream to a much greater
extent than most drugs, so the drugs
become more concentrated inside the
kidney than they are in the blood.
In order for the kidney to eliminate
drugs from the body, the drug must
somehow be prevented from being
reabsorbed from the urine into the
The drug must be chemically changed
into a compound that is less fat-soluble
and therefore less capable of being
This process of converting fat-soluble
drugs into water soluble metabolites
that can be excreted by the kidney is
carried out in the liver.
Usually (but not always) the process of
metabolism decreases the pharmacological
activity of a drug. Even though a
metabolite might remain in the body
(awaiting excretion), it would usually
be pharmacologically inactive or less
active and would not produce the effects
of the parent drug to the same extent.
Many drugs can increase the rate at
which an enzyme system metabolizes a
variety of drugs, thereby increasing the
speed with which a drug is eliminated.
Certain drugs induce an increase in
enzyme activity. This process can
decrease the pharmacological response to
certain agents metabolized in the liver.
For example, phenobarbital stimulates
the production of enzymes that normally
metabolize the anti-coagulant warfarin.
Thus phenobarbital decreases the effect
of warfarin by increasing the metabolism
Some drugs can also stimulate their own
metabolism. This is one mechanism to
explain why increasing doses of a drug
must be administered in order to produce
the same effect that smaller doses
Regarding the placental barrier
referred to earlier, the fetus may
excrete drugs through the umbilical cord
back into the bloodstream of the mother.
The mother can then eliminate the drug
through the liver and kidneys. After
delivery, however, the newborn baby is
no longer attached to the mother and
must deal on its own with any drug in
its blood. Unfortunately, the newborn
baby has few drug metabolizing enzymes
in the liver and the kidneys may not yet
be fully functional. This means, that
the infant has great difficulty
metabolizing and excreting drugs.
Biliary and fecal excretion
Many metabolites of drugs created in
the liver are excreted into the
intestinal tract in the bile. Hence the
intestine is not only a site of
absorption but it is also a site of
The net excretion by this route may be
greatly reduced by subsequent
reabsorption into the bloodstream of
fat-soluble compounds further along the
intestines. In this case drugs will
undergo the process of excretion all
over again and the drug effect is
prolonged. This excretion/reabsorption
phenomenon is called enterohepatic
Metabolites may be excreted in the
feces. More commonly, they are
reabsorbed into the blood and ultimately
excreted in the urine.
Excretion by other routes
Minute amounts of drugs are excreted
into sweat, saliva and tears.
Drugs excreted into the saliva enter
the mouth, where they are usually
swallowed. Their fate thereafter is the
same as drugs taken orally. Some drug
concentrations in the saliva parallel
those found in the plasma.
Since breast milk is more acidic than
blood plasma, basic compounds may become
slightly concentrated in this location.
Although excretion into hair and skin
occurs in small quantities, it does have