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Research ArticleMetabolism, Transport, and Pharmacogenomics

Cynomolgus Monkey as a Potential Model to Assess Drug Interactions Involving Hepatic Organic Anion Transporting Polypeptides (OATPs): In Vitro, In Vivo and In Vitro-to-In Vivo Extrapolation

Hong Shen, Zheng Yang, Gabe Mintier, Yong-Hae Han, Cliff Chen, Praveen Balimane, Mohammed Jemal, Weiping Zhao, Renjie Zhang, Sanjith Kallipatti, Sabariya Selvam, Sunil Sukrutharaj, Prasad Krishnamurthy, Punit Marathe and David A Rodrigues
Journal of Pharmacology and Experimental Therapeutics January 7, 2013, jpet.112.200691; DOI: https://doi.org/10.1124/jpet.112.200691
Hong Shen
1 Bristol-Myers Squibb;
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Zheng Yang
1 Bristol-Myers Squibb;
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Gabe Mintier
1 Bristol-Myers Squibb;
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Yong-Hae Han
1 Bristol-Myers Squibb;
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Cliff Chen
1 Bristol-Myers Squibb;
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Praveen Balimane
1 Bristol-Myers Squibb;
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Mohammed Jemal
1 Bristol-Myers Squibb;
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Weiping Zhao
1 Bristol-Myers Squibb;
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Renjie Zhang
2 WuXi AppTec Co., Ltd;
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Sanjith Kallipatti
3 Bristol-Myers Squibb Biocon R&D Center
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Sabariya Selvam
3 Bristol-Myers Squibb Biocon R&D Center
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Sunil Sukrutharaj
3 Bristol-Myers Squibb Biocon R&D Center
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Prasad Krishnamurthy
3 Bristol-Myers Squibb Biocon R&D Center
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Punit Marathe
1 Bristol-Myers Squibb;
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David A Rodrigues
1 Bristol-Myers Squibb;
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Data Supplement

Files in this Data Supplement:

  • Supplementary Figures -
    Supplementary Figure 1. Alignment of the predicted amino acid sequences of cynomolgus (Cyno), rhesus (Rhes) and human (Huma) OATPs.
    Supplementary Figure 1B. (OATP1B3).
    Supplementary Figure 1C. (OATP2B1).
    Supplementary Figure 2. Concentration dependent uptake rates (A and B), relative contribution of active and passive processes (C and D), and Eadie-Hofstee plots (E and F) of uptake 3HRSV by cynomolgus monkey and human hepatocytes.
    Supplementary Figure 3. Time course of uptake of 3HRSV (1 μM) by HEK 293 cells stably expressing cOATP (A) and hOATP (B).
    Supplementary Figure 4. Individual AUC0-inf (A), and Cmax values (B) of RSV in 3 cynomolgus monkeys after a single oral dose of 3 mg/kg RSV with and without an oral RIF administration (15 mg/kg).

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