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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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