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Today
most drugs are synthesized by chemists in the laboratory.
Synthetic drugs are better controlled than those occurring
naturally, which ensures that each dose imparts the same effect.
Some new synthetic drugs are developed by modifying the structure
of existing substances. These new drugs are called analogues.
For example, prednisone is an analogue of the hormone cortisone
(Hydrocortisone). Because scientists can selectively alter
the drug's structure, analogues may be more effective and
cause fewer side effects than the drugs from which they were
derived.
One of the newer methods for developing drugs involves the
use of gene splicing, or recombinant DNA (Genetic Engineering).
In drug research, this technique joins the DNA of a specific
type of human cell to the DNA of a second organism, usually
a harmless bacterium, to produce a recombinant (or "recombined")
DNA. The altered organism then begins to produce the substance
produced by the human cell. This substance is extracted from
the bacteria and purified for use as a drug.
The first drug produced in this manner was the hormone insulin
in 1982, which was created in large quantities by inserting
the human insulin gene in Escherichia coli (E. coli) bacteria.
Since 1982 other genetically engineered drugs for humans have
been developed, including tissue plasminogen activator (tPA),
an enzyme used to dissolve blood clots in people who have
suffered heart attacks, and erythropoetin, a hormone used
to stimulate the production of red blood cells in people with
severe anemia.
Because of the great expense and time involved, most new drugs
are created by large, well-funded pharmaceutical companies.
From idea to production, the development of a new drug can
take up to ten years and cost about $200 million. The process
usually starts with the idea that an existing chemical substance
has therapeutic value or that the structure of an existing
drug can be modified for new clinical uses. Out of 10,000
chemicals tested in a laboratory, only one may eventually
become a drug.
Once drug researchers have determined that a new substance
may have medical value, an elaborate testing program begins.
The drug is tested first on small animals such as rats and
mice, and then on larger animals such as monkeys and dogs.
If these tests indicate that the new drug is effective against
its intended target-such as a particular disease-and shows
an acceptably low level of toxicity, the drug company requests
permission from the Food and Drug Administration (FDA), an
agency of the U.S. Department of Health and Human Services,
to test the drug in humans.
If the agency approves the request, clinical trials on humans
can begin. These experiments are usually divided into three
phases, each of which can last from several months to several
years. In the first phase, the drug is tested on a small number
of healthy individuals to determine its effect on the body.
The second phase tests the drug on a small number of people
who have the disease or disorder the drug manufacturer hopes
the drug will treat. These individuals are divided into two
groups: those who receive the drug and those who receive a
placebo, or inactive compound. Neither the investigating physicians
nor the members of the test group know who is receiving the
drug or who is receiving the placebo. This technique, called
a double-blind study, ensures that no one consciously or unconsciously
influence the drug's effect. The third phase tests the drug
on a much larger group of people and determines specific doses,
possible interactions with other drugs, responses related
to gender, and other information used for drug labeling. At
the end of the third phase, a drug manufacturer compiles the
results of the clinical trials and submits them to the FDA
in a new product application. If the drug has been proven
effective and safe, and its benefits outweigh any risks, the
agency approves the drug for marketing. FDA approval of a
new drug may take up to 18 months; however, the agency is
working to reduce the time to 12 months for most drugs and
6 months for highly effective drugs that treat previously
incurable conditions.
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