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Drug Metabolism & Disposition

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Research ArticleArticle

Comparison of methods for estimating unbound intracellular-to-medium concentration ratios in rat and human hepatocytes using statins

Takashi Yoshikado, Kota Toshimoto, Tomohisa Nakada, Kazuaki Ikejiri, Hiroyuki Kusuhara, Kazuya Maeda and Yuichi Sugiyama
Drug Metabolism and Disposition May 3, 2017, dmd.116.074823; DOI: https://doi.org/10.1124/dmd.116.074823
Takashi Yoshikado
1 RIKEN;
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  • For correspondence: ychi.sugiyama@riken.jp tyoshikado@riken.jp
Kota Toshimoto
1 RIKEN;
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Tomohisa Nakada
2 Mitsubishi Tanabe Pharma Corporation;
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Kazuaki Ikejiri
3 University of Tokyo
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Hiroyuki Kusuhara
3 University of Tokyo
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Kazuya Maeda
3 University of Tokyo
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Yuichi Sugiyama
1 RIKEN;
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  • For correspondence: ychi.sugiyama@riken.jp tyoshikado@riken.jp

Data Supplement

  • Supplemental Data -

    Supplemental Text - Theoretical derivation of the equations for Kp,uu considering the
    plasma membrane potential of cells and the fraction of drugs ionized

    Supplemental Table 1 - Intracellular volumes of rat and human hepatocytes

    Supplemental Figure 1 - The pH-dependent membrane permeation clearance of pitavastatin (A),
    rosuvastatin (B), and pravastatin (C) across Caco-2 cell monolayers was measured in an apical-tobasal
    direction with an apical pH of 5.5, 6.0, 6.5, and 7.4, and a basal pH of 7.4 in the presence of
    rifamycin SV (100 mu-M), cyclosporin A (10 mu-M), and Ko143 (10 mu-M)

    Supplemental Figure 2 - Concentration-dependent uptake of pitavastatin (A), rosuvastatin (B), and
    pravastatin (C) by rat hepatocytes

    Supplemental Figure 3 - Concentration-dependent uptake of pitavastatin (A, D), rosuvastatin (B, E),
    and pravastatin (C) by human hepatocytes

  View article

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