Download Penicillin

Group Members:
Chan Man Kin, So Chun Yan, Tsang Ka Kui,
Wong Chi Hang, Yip Pak Fung (7S)
Topic: Drug (Penicillin)
Introduction:
Penicillin (sometimes abbreviated PCN or pen) is a group of
Beta-lactam antibiotics used in the treatment of bacterial
infections caused by susceptible, usually Gram-positive,
organisms. “Penicillin” is also the informal name of a specific
member of the penicillin group Penam Skeleton, which has the
molecular formula R-C9H11N2O4S, where R is a variable side
chain.
Stages of development:
Lead compound discovery
During the 1920’s the Scotsman Sir Alexander Fleming, a
bacteriologist noticed a halo of inhibition of bacterial growth
around a contaminant blue-green mold Staphylococcus plate
culture. Fleming concluded that the mold was releasing a
substance that was inhibiting bacterial growth and lysing the
bacteria. He grew a pure culture of the mold and discovered that it
was a Penicillium mold.
Molecular modification
After further experiments, Fleming was convinced that
penicillin could not last long enough in the human body to kill
pathogenic bacteria, and stopped studying penicillin after 1931,
but restarted some clinical trials in 1934 and continued to try to
get someone to purify it until 1940. By 1940 he had perfected the
methods for extracting and purifying penicillin. Many saw this as
a very key in the development of penicillin, because it was the
difficulty in obtaining penicillin that had caused Alexander
Fleming to be so unsure about its future.
Formulation development
The availabilty of Penicillin was low while the required dose
was large. Since Penicillin are actively secreted, and about 80% of
a penicillin dose is cleared by secretion within three to four hours
of administration. During those times, it became common
procedure to collect the urine from patients being treated so that
the penicillin could be isolated and reused.
This was not a satisfactory solution, however; so researchers
looked for a way to slow penicillin secretion. They hoped to find a
molecule that could compete with penicillin for the organic acid
transporter responsible for secretion such that the transporter
would preferentially secrete the competitive inhibitor. The
uricosuric agent probenecid proved to be suitable. When
probenecid and penicillin are concomitantly administered,
probenecid competitively inhibits the secretion of penicillin,
increasing penicillin's concentration and prolonging its activity.
However, after the problem of limited supply was solved and
the technique of mass-production was developed, the use of
probenecid declined.
Safety tests and human trials
The first laboratory test was conducted on eight mice with a
streptococcus infection. Four of the mice were injected with
penicillin, and the remaining four were left untreated as controls.
Of the mice treated with penicillin, two survived and the other two,
although they did resist the bacteria, died. The four untreated mice
died within a day.
On February 1, 1941, the first test of penicillin in humans was
conducted. A policeman, who had an advanced staphylococcus
bacterial infection, was treated with penicillin for five days, after
which the penicillin supply ran out. Almost as soon as the
treatment started, the man began to show steady signs of
improvement until the treatment stopped. Although he later died,
it showed that penicillin could be used even in advanced stages of
an infection. It also showed that much more penicillin would be
needed to fully carry out a treatment. That same year, the group
decided to test children, because children would need smaller
doses of the drug. From February to June, five children were
treated with penicillin in stages were other medicines failed. Of
the five, only one died, and an autopsy revealed that it was a result
of an unrelated cause.
Approval for marketing
In the summer of 1941, a way to mass-produce penicillin was
found, production of penicillin could be increased ten-fold by
adding corn steep liquor, a by-product of cornstarch production.
Soon, Alfred N. Richards, chairman of the Committee on Medical
Research of the Office of Scientific Research and Development,
began to take interest in the penicillin developments. He then
convinced three top pharmaceutical manufacturers, Merck and
Company, E. R. Squibb and Sons, and Charles Pfizer Company, to
produce penicillin. By the time WWII had ended, enough
penicillin was produced to meet military needs, and the drug was
just entering the public market.
Conclusion
More than fifty years after its discovery, penicillin is still one
of the most widely used antibiotics today. Because ordinary
penicillin has a limited spectrum of effectiveness, many
derivatives have been developed to increase the usefulness of the
drug. Nevertheless, as time passes, more and more bacteria have
developed resistance to the many forms of the antibiotic that are
available. As a result, much effort is being put into the research of
newer antibiotics that will fight these strains.