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Research ArticleArticle

Selective Mechanism-Based Inactivation of CYP3A4 by CYP3cide (PF-04981517) and Its Utility as an In Vitro Tool for Delineating the Relative Roles of CYP3A4 versus CYP3A5 in the Metabolism of Drugs

Robert L. Walsky, R. Scott Obach, Ruth Hyland, Ping Kang, Sue Zhou, Michael West, Kieran F. Geoghegan, Christopher J. Helal, Gregory S. Walker, Theunis C. Goosen and Michael A. Zientek
Drug Metabolism and Disposition September 2012, 40 (9) 1686-1697; DOI: https://doi.org/10.1124/dmd.112.045302
Robert L. Walsky
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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R. Scott Obach
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Ruth Hyland
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Ping Kang
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Sue Zhou
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Michael West
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Kieran F. Geoghegan
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Christopher J. Helal
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Gregory S. Walker
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Theunis C. Goosen
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Michael A. Zientek
Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
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Article Information

vol. 40 no. 9 1686-1697
DOI 
https://doi.org/10.1124/dmd.112.045302
PubMed 
22645092

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0090-9556
Online ISSN 
1521-009X
History 
  • Received March 6, 2012
  • Accepted May 29, 2012
  • Published online August 17, 2012.

Article Versions

  • Earlier version (May 29, 2012 - 11:17).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics

Author Information

  1. Robert L. Walsky1,
  2. R. Scott Obach,
  3. Ruth Hyland,
  4. Ping Kang,
  5. Sue Zhou2,
  6. Michael West,
  7. Kieran F. Geoghegan,
  8. Christopher J. Helal,
  9. Gregory S. Walker,
  10. Theunis C. Goosen and
  11. Michael A. Zientek
  1. Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Groton, CT (R.L.W., R.S.O., M.W., K.F.G., C.J.H., G.S.W., T.C.G.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., San Diego, CA (S.Z., P.K., M.A.Z.); and Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Pfizer, Inc., Sandwich, United Kingdom (R.H.)
  1. Address correspondence to:
    Michael A. Zientek, Pfizer, Inc., 10777 Science Center Dr., La Jolla, CA 92121. E-mail: michael.zientek{at}pfizer.com
  • ↵1 Current affiliation: AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts.

  • ↵2 Current affiliation: Frontier BioSciences, Inc., Germantown, Maryland.

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Drug Metabolism and Disposition: 40 (9)
Drug Metabolism and Disposition
Vol. 40, Issue 9
1 Sep 2012
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Research ArticleArticle

SELECTIVE INHIBITION OF CYP3A4 BY CYP3cide

Robert L. Walsky, R. Scott Obach, Ruth Hyland, Ping Kang, Sue Zhou, Michael West, Kieran F. Geoghegan, Christopher J. Helal, Gregory S. Walker, Theunis C. Goosen and Michael A. Zientek
Drug Metabolism and Disposition September 1, 2012, 40 (9) 1686-1697; DOI: https://doi.org/10.1124/dmd.112.045302

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Research ArticleArticle

SELECTIVE INHIBITION OF CYP3A4 BY CYP3cide

Robert L. Walsky, R. Scott Obach, Ruth Hyland, Ping Kang, Sue Zhou, Michael West, Kieran F. Geoghegan, Christopher J. Helal, Gregory S. Walker, Theunis C. Goosen and Michael A. Zientek
Drug Metabolism and Disposition September 1, 2012, 40 (9) 1686-1697; DOI: https://doi.org/10.1124/dmd.112.045302
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