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

被引：461

作者：

Morgan, Paul ^{[1
,2
,3
]}

Van der Graaf, Piet H. ^{[1
,2
,3
,4
]}

Arrowsmith, John ^{[5
]}

Feltner, Doug E. ^{[6
]}

Drummond, Kira S. ^{[7
]}

Wegner, Craig D. ^{[8
]}

Street, Steve D. A. ^{[9
]}

机构：

[1] Pfizer Ltd, Dept Pharmacokinet, Sandwich CT13 9NJ, Kent, England

[2] Pfizer Ltd, Dept Dynam, Sandwich CT13 9NJ, Kent, England

[3] Pfizer Ltd, Dept Metab, Sandwich CT13 9NJ, Kent, England

[4] Pfizer Ltd, Pharmacometr Global Clin Pharmacol, Sandwich CT13 9NJ, Kent, England

[5] Pfizer Ltd, Portfolio Management, Sandwich CT13 9NJ, Kent, England

[6] Pfizer Ltd, Translat Med, Sandwich CT13 9NJ, Kent, England

[7] Pfizer Ltd, Dev Operat, Sandwich CT13 9NJ, Kent, England

[8] Pfizer Ltd, Indicat Discovery, Sandwich CT13 9NJ, Kent, England

[9] Pfizer Ltd, Res Ctr Excellence, Sandwich CT13 9NJ, Kent, England

来源：

DRUG DISCOVERY TODAY | 2012年 / 17卷 / 9-10期

关键词：

CHEMOKINE RECEPTOR CCR5; DRUG DEVELOPMENT; IN-VIVO; HIV-1; INFECTION; ANTAGONIST; MARAVIROC; DISEASE; RATES; INDIVIDUALS; UK-427,857;

D O I：

10.1016/j.drudis.2011.12.020

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：419 / 424

页数：6

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