Accelerating the Process of Drug Discovery

  • A. M. Davis
  • J. Dixon
  • C. J. Logan
  • D. W. Payling
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 37)


This introductory chapter is intended to provide a close examination of the role of drug metabolism and pharmacokinetics (DMPK) in accelerating the drug discovery process. In concentrating on this aspect, however, it is impossible to separate the role and importance of physical properties of the compounds under study. Whilst biological screening provides information of the effect of the compound on the biological system, DMPK data give a feedback of the effect of the biological system on the compound. The importance of physical properties in this will be highlighted. To do justice to this we have had to omit many other factors. Some of those which will not be discussed include the very important interaction of the discovery departments with other functions within pharmaceutical research and development (R&D). These include, for example, the input of the safety assessment function in an appropriate manner to ensure that early information is available to guide decision-making by discovery management.


Drug Discovery Clearance Mechanism Metabolic Property Lead Optimisation Drug Discovery Process 
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  1. Ajay, Walters WP, Murcko MA (1998) Can we learn to distinguish between “drug-like” and “nondrug-like” molecules? J Med Chem 41: 3314–3324PubMedCrossRefGoogle Scholar
  2. Ajay, Walters WP, Murcko MA (1999) Recognising molecules with drug-like properties. Current Opinion in Chemical Biology 3: 384–387PubMedCrossRefGoogle Scholar
  3. Alper J (1994) Drug discovery on the assembly line. Science 264:1399–1401 Andersen Consulting Annual Report (1996) Approaches to improving drug discovery. Scrip 2278: 13Google Scholar
  4. Chiou WL, Barye A (1998) Linear correlation of the fraction of oral dose ab- sorbed of 64 drugs between humans and rats. Pharm Res 15: 1792–1795PubMedCrossRefGoogle Scholar
  5. Dorsey BD, McDaniel SL, Vacca JP, Guare JP, Darke PL, Zugay JA, Emini EA, Schlief WA (1994) L-735,524: The design of a potent and orally bioavailable HIV protease inhibitor J Med Chem 37: 3443–3451Google Scholar
  6. Drews J (1997) Cost of novel drug development. Scrip World Pharmaceutical News 2283: 8Google Scholar
  7. Houston JB, Carlile DJ (1997) Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices. Drug Metab Rev 29: 891–922PubMedCrossRefGoogle Scholar
  8. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev 23: 2–25CrossRefGoogle Scholar
  9. McAuslane N (1999) Accelerating preclinical development. Vision in Business, Conference 25–26 February, Nice, FranceGoogle Scholar
  10. McGinnity DF, Parker AJ, Soars M, Riley RJ (2000) Automated definition of the enzymology of drug oxidation by the major human drug metabolising cytochrome P450 s. Drug Metab Dispos 28: 1327–1324PubMedGoogle Scholar
  11. Moody GC, Griffin SJ, Mather AN, McGinnity DF, Riley RJ (1999) Fully automated analysis of activities catalyse by the major human liver cytochrome P450 (CYP) enzymes: assessment of human CYP inhibition potential. Xenobiotica 29: 53–75PubMedCrossRefGoogle Scholar
  12. Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ, Wastall P (1997) The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J Pharmacol Exp Ther 283: 46–54PubMedGoogle Scholar
  13. Physician’s Desk Reference (1999) Medical Ergonomics Data Production Company, Montvale, NJ, USAGoogle Scholar
  14. Prentis RA, Lis Y, Walker SR (1988) Pharmaceutical innovation by the seven UK-owned pharmaceutical companies. Br J Clin Pharmacol 25:387–396 RD Insight ( 2001 ), Adis International Ltd, Chester, UKGoogle Scholar
  15. Rowland M, Tozer TN (1995) Clinical pharmacokinetics: concepts and applications, 3rd edn. Lippincott, Philadelphia, p 99Google Scholar
  16. Sadowski J, Kubinyi H (1998) A scoring scheme for discriminating between drugs and nondrugs. J Med Chem 41: 3325–3329PubMedCrossRefGoogle Scholar
  17. Smith DA, van de Waterbeemd H (1999) Pharmacokinetics and metabolism inGoogle Scholar
  18. early drug discovery. Current Opinion in Chemical Biology 3:373–378 Teague SJ, Davis AM, Leeson PD, Oprea T (1999) The design of leadlike combinatorial libraries. Angew Chem Int Ed 38: 2743–2748Google Scholar
  19. Then RL (1993) History and future of antimicrobial diaminopyrimidines. J Chemother (Florence) 5: 361–368Google Scholar
  20. UK Office of Health Economics (1999) Scrip World Pharmaceutical News 2416: 27Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • A. M. Davis
  • J. Dixon
  • C. J. Logan
  • D. W. Payling

There are no affiliations available

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