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Research ArticleArticle

Leveraging of Rifampicin-Dosed Cynomolgus Monkeys to Identify Bile Acid 3-O-Sulfate Conjugates as Potential Novel Biomarkers for Organic Anion-Transporting Polypeptides

Rhishikesh Thakare, Hongying Gao, Rachel E. Kosa, Yi-An Bi, Manthena V. S. Varma, Matthew A. Cerny, Raman Sharma, Max Kuhn, Bingshou Huang, Yiping Liu, Aijia Yu, Gregory S. Walker, Mark Niosi, Larry Tremaine, Yazen Alnouti and A. David Rodrigues
Drug Metabolism and Disposition July 2017, 45 (7) 721-733; DOI: https://doi.org/10.1124/dmd.117.075275
Rhishikesh Thakare
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Hongying Gao
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Rachel E. Kosa
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Yi-An Bi
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Manthena V. S. Varma
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Matthew A. Cerny
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Raman Sharma
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Max Kuhn
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Bingshou Huang
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Yiping Liu
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Aijia Yu
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Gregory S. Walker
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Mark Niosi
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Larry Tremaine
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Yazen Alnouti
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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A. David Rodrigues
Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
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Article Information

vol. 45 no. 7 721-733
DOI 
https://doi.org/10.1124/dmd.117.075275
PubMed 
28396527

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0090-9556
Online ISSN 
1521-009X
History 
  • Received January 28, 2017
  • Accepted April 5, 2017
  • Published online June 2, 2017.

Article Versions

  • Earlier version (April 10, 2017 - 09:37).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics

Author Information

  1. Rhishikesh Thakare,
  2. Hongying Gao,
  3. Rachel E. Kosa,
  4. Yi-An Bi,
  5. Manthena V. S. Varma,
  6. Matthew A. Cerny,
  7. Raman Sharma,
  8. Max Kuhn,
  9. Bingshou Huang,
  10. Yiping Liu,
  11. Aijia Yu,
  12. Gregory S. Walker,
  13. Mark Niosi,
  14. Larry Tremaine,
  15. Yazen Alnouti, and
  16. A. David Rodrigues
  1. Pharmacokinetics, Dynamics & Metabolism, Medicine Design (H.G., R.E.K., Y.B., M.V.S.V., M.A.C., R.S., G.S.W., M.N., L.T., A.D.R.), and Nonclinical Statistics, Pfizer Inc., Groton, Connecticut (M.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska (R. T., Y. A.); and WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai, China (B. H., Y. L., A.Y.)
  1. Address correspondence to:
    Dr. A. David Rodrigues, Pharmacokinetics, Dynamics, & Metabolism, Medicine Design, Eastern Point Road, Bldg 220/002/2565, Mail Stop 8220-2439, Pfizer Inc., Groton, CT 06340. E-mail: a.david.rodrigues{at}pfizer.com
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Drug Metabolism and Disposition: 45 (7)
Drug Metabolism and Disposition
Vol. 45, Issue 7
1 Jul 2017
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Research ArticleArticle

Bile Acid Sulfates as Potential Novel OATP Biomarkers

Rhishikesh Thakare, Hongying Gao, Rachel E. Kosa, Yi-An Bi, Manthena V. S. Varma, Matthew A. Cerny, Raman Sharma, Max Kuhn, Bingshou Huang, Yiping Liu, Aijia Yu, Gregory S. Walker, Mark Niosi, Larry Tremaine, Yazen Alnouti and A. David Rodrigues
Drug Metabolism and Disposition July 1, 2017, 45 (7) 721-733; DOI: https://doi.org/10.1124/dmd.117.075275

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Research ArticleArticle

Bile Acid Sulfates as Potential Novel OATP Biomarkers

Rhishikesh Thakare, Hongying Gao, Rachel E. Kosa, Yi-An Bi, Manthena V. S. Varma, Matthew A. Cerny, Raman Sharma, Max Kuhn, Bingshou Huang, Yiping Liu, Aijia Yu, Gregory S. Walker, Mark Niosi, Larry Tremaine, Yazen Alnouti and A. David Rodrigues
Drug Metabolism and Disposition July 1, 2017, 45 (7) 721-733; DOI: https://doi.org/10.1124/dmd.117.075275
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