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Research ArticleSpecial Section on Prediction of Human Pharmacokinetic Parameters from In Vitro Systems

A Perspective on the Prediction of Drug Pharmacokinetics and Disposition in Drug Research and Development

Li Di, Bo Feng, Theunis C. Goosen, Yurong Lai, Stefanus J. Steyn, Manthena V. Varma and R. Scott Obach
Drug Metabolism and Disposition December 2013, 41 (12) 1975-1993; DOI: https://doi.org/10.1124/dmd.113.054031
Li Di
Pfizer Inc., Groton, Connecticut
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Bo Feng
Pfizer Inc., Groton, Connecticut
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Theunis C. Goosen
Pfizer Inc., Groton, Connecticut
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Yurong Lai
Pfizer Inc., Groton, Connecticut
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Stefanus J. Steyn
Pfizer Inc., Groton, Connecticut
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Manthena V. Varma
Pfizer Inc., Groton, Connecticut
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R. Scott Obach
Pfizer Inc., Groton, Connecticut
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Abstract

Prediction of human pharmacokinetics of new drugs, as well as other disposition attributes, has become a routine practice in drug research and development. Prior to the 1990s, drug disposition science was used in a mostly descriptive manner in the drug development phase. With the advent of in vitro methods and availability of human-derived reagents for in vitro studies, drug-disposition scientists became engaged in the compound design phase of drug discovery to optimize and predict human disposition properties prior to nomination of candidate compounds into the drug development phase. This has reaped benefits in that the attrition rate of new drug candidates in drug development for reasons of unacceptable pharmacokinetics has greatly decreased. Attributes that are predicted include clearance, volume of distribution, half-life, absorption, and drug-drug interactions. In this article, we offer our experience-based perspectives on the tools and methods of predicting human drug disposition using in vitro and animal data.

Footnotes

    • Received August 5, 2013.
    • Accepted September 24, 2013.
  • dx.doi.org/10.1124/dmd.113.054031.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 41 (12)
Drug Metabolism and Disposition
Vol. 41, Issue 12
1 Dec 2013
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Research ArticleSpecial Section on Prediction of Human Pharmacokinetic Parameters from In Vitro Systems

Prediction of Drug Disposition

Li Di, Bo Feng, Theunis C. Goosen, Yurong Lai, Stefanus J. Steyn, Manthena V. Varma and R. Scott Obach
Drug Metabolism and Disposition December 1, 2013, 41 (12) 1975-1993; DOI: https://doi.org/10.1124/dmd.113.054031

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Research ArticleSpecial Section on Prediction of Human Pharmacokinetic Parameters from In Vitro Systems

Prediction of Drug Disposition

Li Di, Bo Feng, Theunis C. Goosen, Yurong Lai, Stefanus J. Steyn, Manthena V. Varma and R. Scott Obach
Drug Metabolism and Disposition December 1, 2013, 41 (12) 1975-1993; DOI: https://doi.org/10.1124/dmd.113.054031
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  • Article
    • Abstract
    • Introduction and History
    • Predicting Half-Life
    • Predicting Volume of Distribution
    • Predicting Clearance
    • Predicting Oral Bioavailability
    • Predicting Drug-Drug Interactions
    • ADME Predictions: The Future
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
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