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Australian Journal of Pharmacy : February 2005
pharmacy pro The birth of ibuprofen pharmacy professional updates To mark the 21st anniversary of when ibuprofen first gained OTC status in the United Kingdom, Professor RIC DAY, Professor of Clinical Pharmacology and chairman of the Drug Development Unit at the School of Medical Sciences, University of NSW in Sydney, interviewed the man credited with discovering and developing ibuprofen, Professor STEWART ADAMS OBE. Professor Adams, now 81 years old, still lives a stone’s throw from the Boots Healthcare research laboratory in Nottingham, England where he worked until he retired in 1983. Professor Day first became interested in ibuprofen while at Kansas University Medical Center when he analysed ibuprofen’s dose response in rheumatoid arthritis patients. Professor Day has also worked with Australian colleagues at St Vincent’s Hospital on the disposition of the enantiomers of ibuprofen. Professor Ric Day (left) interviews Professor Stewart Adams Q I remember visiting the Boots laboratory in Nottingham with fellow University of NSW colleague Ken Williams to discuss our work on enantiomers of ibuprofen. How and when did you first come to start working at the Boots Nottingham laboratory, and what was your first role? My first role at Boots in the UK was as a biologist, just after the war in 1945. I was working on the sterility side at one of the largest surface culture factories in the UK producing penicillin, which Boots man- aged for the government at the time. I then transferred to the Research Department at Boots in 1947, and worked in the field of bio-Assay and developed a new method for the bio-Assay of heparin which became the recommended method in the British Pharmacopoeia for over 20 years. Q Q What were your main areas of interest? My main interest was heparin and I worked on histamine/heparin relation- ships for my doctorate at Leeds Medical School. Tell us about your discovery that anti-inflammatory drugs reduced the erythema caused by UV light on the skin? Little was known about the pharmacology of aspirin. It was thought of as an anal- gesic/antipyretic but there was no animal test by which its analgesic effect could be demonstrated. But I had speculated from my reading that the analgesic effects of aspirin were due to its anti-inflammatory action and that it had some specific effect in inflamed tissue responsible for its value in high doses in rheumatoid arthritis. Eventu- ally, after many failures, I came across the technique of UV erythema in the guinea pig. After a long period of development, I was finally able to show an effect with aspirin in reasonable oral doses. Moreover, the technique seemed very specific for aspirin since steroids and many other phar- macological agents were inactive. The UV erythema test was the basis of all our work but we later added analgesic and antipyretic models. Q Q Do you recall any setbacks that you faced in the lead up to the discovery? As in all research there were many set- backs, one of them being aspirin ana- logues. I had suggested a chemical pro- gram based on modifications to aspirin since, incredibly, no anti-inflammatory studies had ever been conducted on such compounds in more than 50 years since the introduction of aspirin. I felt sure we were bound to find something superior to aspirin. Sadly, wherever compounds were 84 ? THE AUSTRALIAN JOURNAL OF PHARMACY VOL 86 FEBRUARY 2005 Did this discovery aid in your later research with ibuprofen? more potent, they were also more toxic. But even more disappointments were to follow because, remember, we had four clinical failures before ibuprofen. The first compound we sent to clinical trial was inactive, the next three were active but had unacceptable side effects, and only the fifth, ibuprofen, met all objectives. Q When did the first clinical trial of ibuprofen take place and what were the results? It was conducted at the Northern General Hospital in Edinburgh in the Rheumatol- ogy Department...where all of our early trials took place. It was headed by Profes- sor Duthie, one of the leading rheumatol- ogists in the UK. Dr Tom Chalmers pro- duced the final report on the trial in February 1966, which showed that ibuprofen proved active in rheumatoid arthritis at 300mg and 600mg per day. Q Considering the fact that, at the time, the role of prostaglandins had not been described and the mode of action of anti-inflammatory drugs was unknown, were you surprised with the speed of the development of ibuprofen since its discovery? The speed of development seemed very slow to me at the time. It was more than seven years from when it was first made (1961) to being marketed (1969), and 22 years before it became an OTC product. It was, of course, extremely difficult in