The Role of Pharmacokinetics in Drug Discovery: Finding Drug Candidates with the Greatest Potential for Success

  • J. H. Lin
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 37)


Searching for new drugs is an extremely time-consuming and costly endeavor. Much of the time and cost is expended on clinical studies to obtain efficacy and safety data. Many drug candidates fail during these clinical trials. There are three main reasons for clinical failure, namely, lack of efficacy, serious side effects, and unacceptable pharmacokinetics. In a survey by PMA/FDA (1991), approximately 40% of clinical failures were attributable to poor pharmacokinetics, while lack of efficacy and adverse effects accounted for about 30% and 10%, respectively. Obviously, the ability to predict the efficacy, toxicity, and pharmacokinetics from preclinical and in vitro studies can reduce the high incidence of clinical failures and improve the success rate of drug candidates to reach the market. However, prediction of clinical efficacy and toxicity is not easy; in most cases, they can be determined only by clinical experience. In contrast, prediction of human pharmacokinetics is relatively easy. There is an increasing body of evidence to suggest that a reasonable prediction of bioavailability and clearance in humans can be obtained when applying appropriate pharmacokinetic principles (Houston 1994; Iwatsubo et al. 1997; Lave et al. 1999; Lin 1999).


Drug Discovery Drug Candidate Metabolic Clearance Intrinsic Clearance Human Pharmacokinetic 
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© Springer-Verlag Berlin Heidelberg 2002

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  • J. H. Lin

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