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Monday, May 16, 2011


Like most scientists and doctors in this area, I chose a career developing drugs in the hope of improving people's lives. 'Hope' I say, because pharmaceutical research and development is often a source of frustration and disappointment. Certainly, we are continuing contribution to the scientific and medical knowledge, but our work does not always result in new drugs. Very few to get one of us to work on vehicles that ultimately benefit patients.
I was one of those fortunate though. In the two decades of research, I have managed to be in the right place at the right time in more than one occasion. But the development program has been a greater interest and participation in one of the drugs in the world's most famous. Scientific name is sildenafil citrate, but it is better known as Viagra.
I first came across this project in the late 1980s, when I learned colleagues in

the laboratories of Pfizer in Sandwich, a small town on the southeastern coast of England, has come up with a hypothesis about the prohibition of selective enzyme called PDE5. They believed they could produce a drug to prevent PDE5 can expand blood vessels and treatment of angina pectoris. While the purpose of the project was fantastic, and I must admit I was doubtful it would be a breakthrough because they had hoped.
By the early 1990s, and was the team discovered a strong and selective inhibitor of PDE5, known at that time in the United Kingdom 92 480. Tests showed early had a moderate impact on the blood vessels of healthy volunteers, which was promising sign. However, only inhibitor in the body for a relatively short period, and when taken three times a day - to maintain a constant effect - it gave some pain in the muscles of volunteers.

In one of the studies, and volunteers for male erectile dysfunction increased after several days of the initial dose. No one thought of us at Pfizer many of these side effects at that time. I remember thinking that even if it did not work, who want to take the drug on Wednesday to get an erection on Saturday? We paid for it with studies in angina pectoris.
At the time I run one of two clinical trials, Pfizer, near Sandwich, where we

studied whether the United Kingdom 92 480 interacted with nitrates - standard treatment for angina. We found that it did not exaggerate the impact of nitrates, which may cause the blood pressure drops too much. This turned out to be one of the many results which reduced the likelihood of becoming the United Kingdom 92 480 treatment of angina pectoris.
However, it has now been increased erectile dysfunction reported in studies on volunteers more than that, so we decided to follow up on these reports to know that it will take us.
Incidentally, it was almost at the same time, other studies reveal more information about the path of biochemical participate in the erection process. This has helped to understand how the drug can amplify the effects of sexual stimulation in opening up the blood vessels in the penis. With opportunities in the United Kingdom 92 480 for the treatment of angina now slim, we decided to run pilot studies in patients who suffer from erectile dysfunction). In the preliminary study, and watch videos while the exciting device to monitor the ring and solid bars of their own. Initial results were encouraging and showed that the drug was more effective than placebo.
However, we have had there is still a long way to go and a lot of question marks. He said that the drug be effective when used in the preparation of less clinical and after a single dose? How can we measure its effects accurately without being intrusive? The work will be in men who suffer from ED due to various medical conditions, such as high blood pressure, diabetes, heart disease or prostate?
The next trial included more than 300 patients from the United Kingdom, Sweden and France.

We included men with diabetes, to extend the duration of treatment for four weeks and tested three different doses and placebo. Questioned by some doctors in this area that the drug through the mouth can be opened selectively in the blood vessels in the penis, but we persevered, and I remember a distinct air of excitement at the first meeting with the investigators - who were doctors adminstering drugs in the next trial.
It also provides for the trial, and I began to feel more and more nervous the possibility of knowledge of results - not least because we have now spent several millions of dollars on this project until now, was to deliver the drug for use. The investigators reported encouraging results, but to assume that most of these patients were on placebo? We have obtained the right dose? Will patients understand the drug works only with sexual stimulation? Do we have the questionnaires and diaries make it clear enough, and patients will complete correctly? I asked myself all these questions over and over again.
Statisticians in the team is the first to see the data - it's important to analyze the results and verify the figures. People are being careful, and they do not like to exchange information so they are quite confident of the results. I remember a desperate attempt to read the language of statistical our leadership in the body in the days before the results. But it was distinctive deadpan and I was able to deduce something from his behavior.
When the results came at the end of the day through it exceeded the wildest expectations we have. There was a correlation between dose and response beautiful, with about 90 per cent of patients responding at the highest dose. This drug was also well tolerated, with a very small number of patients reporting pain in the muscles and a very small number of school drop-out. Diaries and questionnaires also provided accurate results and consistent. Impossible not to feel the thrill and excitement at this stage of the study, and I'm not sure.
But the nature of drug development means that you can not taste the highest level for a long time. We were preparing to embark on the most expensive stage of drug development - clinical trials, long-term for thousands of patients in all parts of the world. This requires hundreds of millions of dollars - and we still did not get a chance and only one out of every five of the drug to pass these tests and obtain a license. Therefore, the company will continue to fund a project we have?
The program has already attracted some unexpected publicity, and I am concerned what impact this may have on this resolution. Fortunately, he had written a large number of those who suffer from impotence to us how the situation has had devastating effects on their relationships, and how they were desperate for effective treatment. These letters, and convinced us there is also an urgent need for the treatment of ED and encouraged us to continue to pay the program internally.
We have received funding from the outside and as we continue the clinical program and found the results were better and better. And worked well in the men drug with a variety of causes of ED, including diabetes and spinal cord injury. It also continued to be well tolerated.
12 years after the project began, eight years after the first synthesis of the year in the United Kingdom 92 480 and four after the pilot study the first ED, we had enough information and finally to be confident of the best dose, and drug safety and effectiveness. We applied for a license from the regulatory authorities in 1997.
The rest, as they say, is history. Are being prescribed Viagra for some men 30000000 in all parts of the world. It's very rewarding to see our work has benefited many people. It is this fact that makes the long days and frustration, which is an integral part of development, and drugs intolerable.
I would like to remind myself that I have just one member of a great team - in about 100 specialties of experts to have played a role in making Viagra available to patients. Like many successful scientists, I have had my fair share of luck.