Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving Phase II survival

Drug Discov Today. 2012 May;17(9-10):419-24. doi: 10.1016/j.drudis.2011.12.020. Epub 2011 Dec 29.


In an effort to uncover systematic learnings that can be applied to improve compound survival, an analysis was performed on data from Phase II decisions for 44 programs at Pfizer. It was found that not only were the majority of failures caused by lack of efficacy but also that, in a large number of cases (43%), it was not possible to conclude whether the mechanism had been tested adequately. A key finding was that an integrated understanding of the fundamental pharmacokinetic/pharmacodynamic principles of exposure at the site of action, target binding and expression of functional pharmacological activity (termed together as the 'three Pillars of survival') all determine the likelihood of candidate survival in Phase II trials and improve the chance of progression to Phase III.

MeSH terms

  • Aminopyridines / pharmacology
  • Aminopyridines / therapeutic use
  • Animals
  • CCR5 Receptor Antagonists
  • Clinical Trials, Phase II as Topic*
  • Cyclohexanes / pharmacology
  • Cyclohexanes / therapeutic use
  • Drug Evaluation*
  • HIV Infections / drug therapy
  • HIV Infections / metabolism
  • Humans
  • Maraviroc
  • Morpholines / pharmacology
  • Morpholines / therapeutic use
  • Neuralgia / drug therapy
  • Neuralgia / metabolism
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics*
  • Receptors, Dopamine D3 / agonists
  • Sexual Dysfunction, Physiological / drug therapy
  • Sexual Dysfunction, Physiological / metabolism
  • Triazoles / pharmacology
  • Triazoles / therapeutic use


  • Aminopyridines
  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • Morpholines
  • PF 592379
  • Pharmaceutical Preparations
  • Receptors, Dopamine D3
  • Triazoles
  • Maraviroc