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Research ArticleArticle

Prediction of Transporter-Mediated Rosuvastatin Hepatic Uptake Clearance and Drug Interaction in Humans Using Proteomics-Informed REF Approach

Vineet Kumar, Mengyue Yin, Kazuya Ishida, Laurent Salphati, Cornelis E.C.A. Hop, Christopher Rowbottom, Guangqing Xiao, Yurong Lai, Anita Mathias, Xiaoyan Chu, W. Griffith Humphreys, Mingxiang Liao, Zsuzsanna Nerada, Nóra Szilvásy, Scott Heyward and Jashvant D. Unadkat
Drug Metabolism and Disposition February 2021, 49 (2) 159-168; DOI: https://doi.org/10.1124/dmd.120.000204
Vineet Kumar
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Mengyue Yin
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Kazuya Ishida
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Laurent Salphati
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Cornelis E.C.A. Hop
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Christopher Rowbottom
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Guangqing Xiao
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Yurong Lai
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Anita Mathias
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Xiaoyan Chu
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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W. Griffith Humphreys
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Mingxiang Liao
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Zsuzsanna Nerada
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Nóra Szilvásy
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Scott Heyward
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Jashvant D. Unadkat
Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
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Article Information

vol. 49 no. 2 159-168
DOI 
https://doi.org/10.1124/dmd.120.000204
PubMed 
33051248

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0090-9556
Online ISSN 
1521-009X
History 
  • Received August 4, 2020
  • Accepted September 24, 2020
  • Published online January 27, 2021.

Article Versions

  • Earlier version (October 13, 2020 - 16:26).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics

Author Information

  1. Vineet Kumar,
  2. Mengyue Yin,
  3. Kazuya Ishida1,
  4. Laurent Salphati,
  5. Cornelis E.C.A. Hop,
  6. Christopher Rowbottom,
  7. Guangqing Xiao2,
  8. Yurong Lai,
  9. Anita Mathias,
  10. Xiaoyan Chu,
  11. W. Griffith Humphreys3,
  12. Mingxiang Liao4,
  13. Zsuzsanna Nerada,
  14. Nóra Szilvásy,
  15. Scott Heyward, and
  16. Jashvant D. Unadkat
  1. Department of Pharmaceutics, University of Washington, Seattle, Washington (V.K., M.Y., K.I., J.D.U.); Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, California (L.S., C.E.C.A.H.); DMPK, Biogen Idec, Cambridge, Massachusetts (C.R., G.X.); Clinical Pharmacology (A.M.) and Drug Metabolism (Y.L.), Gilead Sciences, Inc., Foster City, California; Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co. Inc., Kenilworth, New Jersey (X.C.); Bristol-Myers Squibb Company, Princeton, New Jersey (W.G.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); SOLVO Biotechnology, Budaörs, Hungary (Z.N., N.S.); and BioIVT, Baltimore, Maryland (S.H.)
  1. Address correspondence to:
    Jashvant D. Unadkat, Department of Pharmaceutics, University of Washington, P.O. Box 357610, Seattle, WA 98195. E-mail: jash{at}uw.edu
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Drug Metabolism and Disposition: 49 (2)
Drug Metabolism and Disposition
Vol. 49, Issue 2
1 Feb 2021
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Research ArticleArticle

IVIVE of Rosuvastatin Hepatic Clearance in Human

Vineet Kumar, Mengyue Yin, Kazuya Ishida, Laurent Salphati, Cornelis E.C.A. Hop, Christopher Rowbottom, Guangqing Xiao, Yurong Lai, Anita Mathias, Xiaoyan Chu, W. Griffith Humphreys, Mingxiang Liao, Zsuzsanna Nerada, Nóra Szilvásy, Scott Heyward and Jashvant D. Unadkat
Drug Metabolism and Disposition February 1, 2021, 49 (2) 159-168; DOI: https://doi.org/10.1124/dmd.120.000204

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Research ArticleArticle

IVIVE of Rosuvastatin Hepatic Clearance in Human

Vineet Kumar, Mengyue Yin, Kazuya Ishida, Laurent Salphati, Cornelis E.C.A. Hop, Christopher Rowbottom, Guangqing Xiao, Yurong Lai, Anita Mathias, Xiaoyan Chu, W. Griffith Humphreys, Mingxiang Liao, Zsuzsanna Nerada, Nóra Szilvásy, Scott Heyward and Jashvant D. Unadkat
Drug Metabolism and Disposition February 1, 2021, 49 (2) 159-168; DOI: https://doi.org/10.1124/dmd.120.000204
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