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Late-occurring and Long-circulating Metabolites of GABAAα2,3 Receptor Modulator AZD7325 Involving Metabolic Cyclization and Aromatization: Relevance to MIST Analysis and Application for Patient Compliance

Chungang Gu, Markus Artelsmair, Charles S. Elmore, Richard J. Lewis, Patty Davis, James E. Hall, Bruce T. Dembofsky, Greg Christoph, Mark A. Smith, Marc Chapdelaine and Maria Sunzel
Drug Metabolism and Disposition March 2018, 46 (3) 303-315; DOI: https://doi.org/10.1124/dmd.117.078873
Chungang Gu
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Markus Artelsmair
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Charles S. Elmore
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Richard J. Lewis
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Patty Davis
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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James E. Hall
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Bruce T. Dembofsky
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Greg Christoph
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Mark A. Smith
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Marc Chapdelaine
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Maria Sunzel
DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
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Article Information

vol. 46 no. 3 303-315
DOI 
https://doi.org/10.1124/dmd.117.078873
PubMed 
29311137

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0090-9556
Online ISSN 
1521-009X
History 
  • Received October 8, 2017
  • Accepted January 3, 2018
  • Published online February 14, 2018.

Article Versions

  • Earlier version (January 8, 2018 - 05:53).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2018 by The Author(s) This is an open access article distributed under the CC BY Attribution 4.0 International license.

Author Information

  1. Chungang Gu,
  2. Markus Artelsmair,
  3. Charles S. Elmore,
  4. Richard J. Lewis,
  5. Patty Davis,
  6. James E. Hall,
  7. Bruce T. Dembofsky,
  8. Greg Christoph,
  9. Mark A. Smith,
  10. Marc Chapdelaine, and
  11. Maria Sunzel
  1. DMPK, IMED Oncology, AstraZeneca, Waltham, Massachusetts (C.G); Early Chemical Development, IMED Pharmaceutical Sciences, AstraZeneca, Mölndal, Sweden (M.A., C.S.E); Medicinal Chemistry, IMED Respiratory Inflammation and Autoimmunity, AstraZeneca, Mölndal, Sweden (R.J.L.); and Legacy R&D at Wilmington, AstraZeneca, Wilmington, Delaware (C.G., C.S.E., P.D., J.E.H., B.T.D., G.C., M.A.S., M.C., M.S.)
  1. Address correspondence to:
    Dr. Chungang Gu, Biogen, Drug Metabolism and Pharmacokinetics, 125 Broadway, Bldg. 8, Cambridge, MA 02142. E-mail: chuck.gu{at}biogen.com
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Drug Metabolism and Disposition: 46 (3)
Drug Metabolism and Disposition
Vol. 46, Issue 3
1 Mar 2018
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AZD7325 Metabolites Involving Cyclization and Aromatization

Chungang Gu, Markus Artelsmair, Charles S. Elmore, Richard J. Lewis, Patty Davis, James E. Hall, Bruce T. Dembofsky, Greg Christoph, Mark A. Smith, Marc Chapdelaine and Maria Sunzel
Drug Metabolism and Disposition March 1, 2018, 46 (3) 303-315; DOI: https://doi.org/10.1124/dmd.117.078873

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AZD7325 Metabolites Involving Cyclization and Aromatization

Chungang Gu, Markus Artelsmair, Charles S. Elmore, Richard J. Lewis, Patty Davis, James E. Hall, Bruce T. Dembofsky, Greg Christoph, Mark A. Smith, Marc Chapdelaine and Maria Sunzel
Drug Metabolism and Disposition March 1, 2018, 46 (3) 303-315; DOI: https://doi.org/10.1124/dmd.117.078873
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