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Research ArticlePerspective

Contribution of Metabolites to P450 Inhibition–Based Drug–Drug Interactions: Scholarship from the Drug Metabolism Leadership Group of the Innovation and Quality Consortium Metabolite Group

Hongbin Yu, Suresh K. Balani, Weichao Chen, Donghui Cui, Ling He, W. Griffith Humphreys, Jialin Mao, W. George Lai, Anthony J. Lee, Heng-Keang Lim, Christopher MacLauchlin, Chandra Prakash, Sekhar Surapaneni, Susanna Tse, Alana Upthagrove, Robert L. Walsky, Bo Wen and Zhaopie Zeng
Drug Metabolism and Disposition April 2015, 43 (4) 620-630; DOI: https://doi.org/10.1124/dmd.114.059345
Hongbin Yu
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Suresh K. Balani
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Weichao Chen
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Donghui Cui
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Ling He
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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W. Griffith Humphreys
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Jialin Mao
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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W. George Lai
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Anthony J. Lee
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Heng-Keang Lim
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Christopher MacLauchlin
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Chandra Prakash
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Sekhar Surapaneni
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Susanna Tse
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Alana Upthagrove
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Robert L. Walsky
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Bo Wen
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Zhaopie Zeng
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
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Article Information

vol. 43 no. 4 620-630
DOI 
https://doi.org/10.1124/dmd.114.059345
PubMed 
25655830

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0090-9556
Online ISSN 
1521-009X
History 
  • Received May 30, 2014
  • Accepted January 27, 2015
  • Published online March 2, 2015.

Article Versions

  • Earlier version (February 5, 2015 - 07:23).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics

Author Information

  1. Hongbin Yu,
  2. Suresh K. Balani,
  3. Weichao Chen,
  4. Donghui Cui,
  5. Ling He,
  6. W. Griffith Humphreys,
  7. Jialin Mao,
  8. W. George Lai,
  9. Anthony J. Lee,
  10. Heng-Keang Lim,
  11. Christopher MacLauchlin,
  12. Chandra Prakash,
  13. Sekhar Surapaneni,
  14. Susanna Tse,
  15. Alana Upthagrove,
  16. Robert L. Walsky1,
  17. Bo Wen2, and
  18. Zhaopie Zeng
  1. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut (H.Y.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (S.K.B.); Vertex Pharmaceuticals, San Diego, California (W.C.); Merck Research Laboratories, West Point, Pennsylvania (D.C.); Daiichi Sankyo, Inc. Edison, New Jersey (L.H.); Bristol-Myers Squibb, Princeton, New Jersey (W.G.H.); Genentech, South San Francisco, California (J.M.); Eisai Pharmaceuticals, Andover, Massachusetts (W.G.L.); AbbVie, North Chicago, Illinois (A.J.L.); Janssen Research and Development, Spring House, Pennsylvania (H.-K.L.); GlaxoSmithKline, Research Triangle Park, North Carolina (C.M.); Biogen Idec, Cambridge, Massachusetts (C.P.); Celgene Corporation, Summit, New Jersey (S.S.); Pfizer Inc., Groton, Connecticut (S.T.); Novartis Pharmaceuticals Corporation, East Hanover, New Jersey (A.U.); AstraZeneca, Waltham, Massachusetts (R.L.W.); Department of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, Palo Alto, California (B.W.); and Sanofi, Bridgewater, New Jersey (Z.Z.)
  1. Address correspondence to:
    Hongbin Yu, Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877. E-mail: hongbin.yu{at}boehringer-ingelheim.com
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Drug Metabolism and Disposition: 43 (4)
Drug Metabolism and Disposition
Vol. 43, Issue 4
1 Apr 2015
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Contribution of Metabolites to P450 Inhibition–Based Drug–Drug Interactions: Scholarship from the Drug Metabolism Leadership Group of the Innovation and Quality Consortium Metabolite Group
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Research ArticlePerspective

Contribution of Metabolites to P450 Inhibition–Based DDIs

Hongbin Yu, Suresh K. Balani, Weichao Chen, Donghui Cui, Ling He, W. Griffith Humphreys, Jialin Mao, W. George Lai, Anthony J. Lee, Heng-Keang Lim, Christopher MacLauchlin, Chandra Prakash, Sekhar Surapaneni, Susanna Tse, Alana Upthagrove, Robert L. Walsky, Bo Wen and Zhaopie Zeng
Drug Metabolism and Disposition April 1, 2015, 43 (4) 620-630; DOI: https://doi.org/10.1124/dmd.114.059345

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Research ArticlePerspective

Contribution of Metabolites to P450 Inhibition–Based DDIs

Hongbin Yu, Suresh K. Balani, Weichao Chen, Donghui Cui, Ling He, W. Griffith Humphreys, Jialin Mao, W. George Lai, Anthony J. Lee, Heng-Keang Lim, Christopher MacLauchlin, Chandra Prakash, Sekhar Surapaneni, Susanna Tse, Alana Upthagrove, Robert L. Walsky, Bo Wen and Zhaopie Zeng
Drug Metabolism and Disposition April 1, 2015, 43 (4) 620-630; DOI: https://doi.org/10.1124/dmd.114.059345
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  • Article
    • Abstract
    • Introduction
    • Risk Assessment of Contribution of Metabolites to P450 Inhibition–Based DDIs Using Literature Data
    • Contribution of Metabolites to P450 Inhibition–Based DDIs for the 137 Most Frequently Prescribed Drugs
    • Review of Current Literature Approaches to Trigger In Vitro DDI Studies for Metabolites
    • Utility of Structural Alerts in Assessing P450 Inhibition and Inactivation Potential of Metabolites
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
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