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Research ArticleArticle

Comparative Evaluation of Plasma Bile Acids, Dehydroepiandrosterone Sulfate, Hexadecanedioate and Tetradecanedioate with Coproporphyrins I and III as Markers of OATP Inhibition in Healthy Subjects

Hong Shen, Weiqi Chen, Dieter M Drexler, Sandhya Mandlekar, Vinay K Holenarsipur, Eric E Shields, Robert Langish, Kurex Sidik, Jinping Gan, W Griffith Humphreys, Punit Marathe and Yurong Lai
Drug Metabolism and Disposition June 2, 2017, dmd.117.075531; DOI: https://doi.org/10.1124/dmd.117.075531

  • Supplemental Data -

    Supplementary Table 1: MS Conditions and LC Retention Times of the 24 Analytes. Groups of Structurally Similar BA are Computed and Assessed against A Suitable Deuterium-Labeled BA.

    Supplementary Table 2: Mean Bile Acid Plasma Concentrations (mean ± SD; n = 7-8) during RIF (Period 1), RSV (Period 2), and Co-administration of RIF and RSV (Period 3).

    Supplementary Table 3: Mean DHEAS Plasma Concentrations (mean ± SD; n = 7-8) during RIF (Period 1), RSV (Period 2), and Co-administration of RIF and RSV (Period 3).

    Supplementary Table 4: Mean HDA and TDA Plasma Concentrations (mean ± SD; n = 7-8) during RIF (Period 1), RSV (Period 2), and Co-administration of RIF and RSV (Period 3).

    Supplementary Figure 1: Transport of CPs I and III by OAT1, OAT2, OAT3, and OAT4. Uptake of 1 μM CP I (A), CP III (B), [3H]para-aminohippuric acid (C), [3H]penciclovir (D), and [3H]estrone-3-sulfate (E) was assessed at 5 min in mock vector-, OAT1-, OAT2-, OAT3-, or OAT4-stably transfected HEK cells in the absence and presence of 1 mM probenecid. Results are the mean ± SD of 3 separate determinations (***p < 0.001 statistically significant difference compared to Mock-HEK cells).

    Supplementary Figure 2: Transport of CPs I and III by OCT2, MATE1, and MATE2K. Uptake of 1 μM CP I (A and C), 1 μM CP III (B and D), 2 μM [14C]metformin (E and F) was assessed at 5 min in mock vector-, OCT2-, MATE1-, or MATE2K-stably transfected HEK cells in the absence and presence of 100 μM pyrimethamine or 200 μM quinidine. Results are the mean ± SD of 3 separate determinations (***p < 0.001 statistically significant difference compared to Mock-HEK cells).

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