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IX. Population Toxicokinetics |
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X. Summary |
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References |
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The pharmaceutical companies throughout the world are undergoing the biggest upheaval in their history. With mergers and buy outs, thousands of jobs have been lost and analysts feel that many small companies without a certain critical mass will either be swallowed up by the bigger fish or just sink to the bottom of the pool and disappear. In contrast, the larger companies have realized that they cannot afford to invest increasingly large amounts on research and not only are they critically appraising staffing levels, but also the questionable need of certain currently undertaken development studies. Costs are continuing to increasea new drug costs between $200300 millionbut the returns in terms of new drugs are falling as governments everywhere are cutting their health care expenditures. Only a small fraction of drugs synthesized enter development and it has been estimated by analysts at Lehmann Brothers that less than 3% of all drugs that do finally reach the market achieve sales figures of $500 million within 5 years, the figures necessary to make the total investment worthwhile. |
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It has been previously considered that many drugs fail before they reach the clinical stage, and indeed, an earlier analysis of UK companies [1] suggested that more than 33% failed due to problems of kinetics, particularly absorption. More recent analysis [2] of North American companies has indicated that overall 68% of drugs fail during clinical trials, particularly those for CNS diseases, whilst drugs with clear efficacy endpoints, such as anti-infectives, are more likely to succeed. |
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There is therefore an increasing realization that preclinical studies must be reevaluated in terms of absolute needs and, with this in mind, recent draft guidelines were prepared for discussion at the Third International Conference on Harmonization (ICH3) in Japan in November 1995. These have reexamined the timings and minimal animal studies necessary to go rapidly into man for the first time without loss of safety. Unfortunately these guidelines do not address the need for preclinical biodisposition studies. There is thus no harmonized advice on this topic [3] despite the fact that such information is a cornerstone of drug development. New toxicokinetic guidelines [4] have provided a basis for taking a fresh look at which preclinical studies are absolutely necessary and seeing if we can incorporate new approaches to this discipline. |
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