The remarkable story of Dr Akira Endo ’ s statin evolution |
administered to dogs at what Dr Endo said were “ astonishingly high levels ” — 200mg / kg / day for two years or 200 times the dose for human subjects .
It was said the drug was
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which became the first commercially available statin in the world .
It was around this time that Professor Stephen Nicholls was finishing medical school and undertaking
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came to the animal |
activity increased 8-10 fold . |
causing lymphoma . The |
his cardiology training . |
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experiments , it did not seem |
For rats , the drug was mak- |
alarm was sufficient for the |
The immediate past pres- |
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to work , or at least , did not |
ing the situation worse . |
drug company funding the |
ident of the Cardiac Society |
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work in the rats who were fed a compactin-enhanced diet for seven days but with |
Clinical trials
Once this was understood ,
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work to discontinue the battle to bring compactin to market . |
of Australia and New Zealand said : “ There is no other class of agents that have |
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no reduction in serum cho- |
it meant that more animal |
Given the money that |
transformed the prevention |
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lesterol detected .
“ With these results , there was no hope of convincing the biologists of evaluating
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experiments could be run . It was shortly after the success of compactin in chickens ( laying hens experienced |
Professor Stephen Nicholls . |
could be made from a commercial version of a drug that promised to reduce strokes and CVD , others |
of CVD in the same way as statins have .”
For him , they changed medicine and people ’ s lives
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compactin … in other animal |
a 50 % reduction in plasma |
were already on the hunt for |
forever in the same way as |
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species like dogs and mon- |
cholesterol after one month ) |
muscles ] was observed . Both |
patients with familial |
statins of their own . |
penicillin and aspirin . |
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keys . It looked as if two years |
that the first clinical study |
adverse effects were revers- |
hypercholesterolaemia |
and |
Although there were |
In Australia , the first |
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of work and over 6000 tests |
happened . |
ible on discontinuation of |
three patients with com- |
stops and starts , con- |
statins became available in |
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had led nowhere .” |
“ In February 1978 , [ phy- |
treatment . |
bined hyperlipidaemia with |
cerns about the side effects |
the early 1990s , initially on |
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It took a further two |
sician Dr Akira ] Yamamoto |
“ While the cholesterol |
compactin . |
were finally erased in 1984 |
authority script . By 1999 , |
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years to show what was happening .
Dr Endo and his team found that if serum levels were assessed 3-7 hours following a single dose , the serum cholesterol reduc-
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started treating an 18-yearold woman with severe familial hypercholesterolaemia ,” Dr Endo said .
“ Her serum cholesterol dropped from 1000mg per decilitre to ∼700mg per deci-
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levels of the patient were not reduced as expected , tuberous and Achilles tendon xan- |
‘ Statins have changed the lives of patients forever .’
“ T h e i r cholesterol declined by roughly 30 % on average ; no severe side effects
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through a series of longterm toxicity studies sponsored by Merck of its drug lovastatin . Again carried out on dogs , it showed the drug still dramatically reduced cholesterol levels but with- |
there were five statins on the market : simvastatin , pravastatin , fluvastatin , cerivastatin and atorvastatin .
They are now used by around one in 10 Australian adults .
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tions could be seen . |
litre during treatment with |
thomatosis was markedly |
were noted . We published |
out the detection of any |
Many believe Dr Endo |
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But at eight hours , |
compactin at a daily dose of |
reduced after treatment at |
these studies in a medical |
tumours . |
deserved a Nobel prize for |
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hepatic HMG-CoA reduc- |
500mg . |
200mg of compactin for five |
journal in 1980 .” |
Merck then submitted |
his groundbreaking work . |
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tase activity was being |
“ But after treatment for |
months .” |
There were complica- |
its application for US Food |
The problem was that Bloch |
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induced in the rats in reac- |
two weeks , transaminase |
He said in the following |
tions , which clearly irritated |
and Drug Administration |
and Feodor Lynen had been |
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tion to the effect of the drug . |
levels of blood were ele- |
six months , Dr Yamamoto |
Dr Endo . |
approval . As a result , it was |
awarded a Nobel prize for |
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When given repeatedly , this |
vated , and [ dystrophy of the |
treated five heterozygous |
The drug had been |
lovastatin , not compactin , |
their work on the regulation |
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