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Research ArticleArticle

An Evaluation of the Dilution Method for Identifying Metabolism-Dependent Inhibitors of Cytochrome P450 Enzymes

Andrew Parkinson, Faraz Kazmi, David B. Buckley, Phyllis Yerino, Brandy L. Paris, Jeff Holsapple, Paul Toren, Steve M. Otradovec and Brian W. Ogilvie
Drug Metabolism and Disposition August 2011, 39 (8) 1370-1387; DOI: https://doi.org/10.1124/dmd.111.038596
Andrew Parkinson
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Faraz Kazmi
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David B. Buckley
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Phyllis Yerino
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Brandy L. Paris
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Jeff Holsapple
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Paul Toren
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Steve M. Otradovec
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Brian W. Ogilvie
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Article Information

vol. 39 no. 8 1370-1387
DOI 
https://doi.org/10.1124/dmd.111.038596
PubMed 
21525169

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0090-9556
Online ISSN 
1521-009X
History 
  • Received February 7, 2011
  • Accepted April 27, 2011
  • Published online July 18, 2011.

Article Versions

  • Earlier version (April 27, 2011 - 07:45).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics

Author Information

  1. Andrew Parkinson,
  2. Faraz Kazmi,
  3. David B. Buckley,
  4. Phyllis Yerino,
  5. Brandy L. Paris,
  6. Jeff Holsapple,
  7. Paul Toren,
  8. Steve M. Otradovec and
  9. Brian W. Ogilvie
  1. XenoTech, LLC, Lenexa, Kansas
  1. Address correspondence to:
    Dr. Andrew Parkinson, XenoTech, LLC, 16825 West 116th Street, Lenexa, KS 66219. E-mail: aparkinson{at}xenotechllc.com
  1. Parts of this work were previously presented at the following meetings: Parkinson A (2009) Metabolism-dependent inhibition (MDI) studies: ten things worth knowing and Paris BL, Kazmi F, Buckley DB, Ogilvie BW, Gipson AE, and Parkinson A (2009) Pitfalls in the design of CYP inhibition studies incorporating a dilution step to examine time-dependent inhibition (TDI) or metabolism-dependent inhibition (MDI). Sixteenth North American Regional ISSX Meeting; 2009 Oct 18–22; Baltimore, MD. International Society for the Study of Xenobiotics, Washington, DC; Buckley DB, Kazmi F, Yerino P, Toren P, Holsapple J, Ogilvie BW, Paris BL, and Parkinson A (2010) Pitfalls in the design of metabolism-dependent CYP inhibition (MDI) experiments with a dilution step: inhibitor depletion by metabolism and/or microsomal binding leads to underestimation of the shifted IC50 value. Ninth International ISSX Meeting; 2010 Sept 4–8; Istanbul, Turkey. International Society for the Study of Xenobiotics, Washington, DC.

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Drug Metabolism and Disposition: 39 (8)
Drug Metabolism and Disposition
Vol. 39, Issue 8
1 Aug 2011
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Research ArticleArticle

An Evaluation of the Dilution Method for Identifying Metabolism-Dependent Inhibitors of Cytochrome P450 Enzymes

Andrew Parkinson, Faraz Kazmi, David B. Buckley, Phyllis Yerino, Brandy L. Paris, Jeff Holsapple, Paul Toren, Steve M. Otradovec and Brian W. Ogilvie
Drug Metabolism and Disposition August 1, 2011, 39 (8) 1370-1387; DOI: https://doi.org/10.1124/dmd.111.038596

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Research ArticleArticle

An Evaluation of the Dilution Method for Identifying Metabolism-Dependent Inhibitors of Cytochrome P450 Enzymes

Andrew Parkinson, Faraz Kazmi, David B. Buckley, Phyllis Yerino, Brandy L. Paris, Jeff Holsapple, Paul Toren, Steve M. Otradovec and Brian W. Ogilvie
Drug Metabolism and Disposition August 1, 2011, 39 (8) 1370-1387; DOI: https://doi.org/10.1124/dmd.111.038596
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