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. 2018 Oct 22;8:15568. doi: 10.1038/s41598-018-33834-9

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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The uptake of compound 1 and GA into rat kidney slice (A,B) and MDCK II cells expressing OAT1 or 3 (C,D). GA (200 mg/kg) was administered orally to both sexes of EHBRs, and plasma was collected 12 hr after oral administration. The concentrations of compound 1 and GA in pooled plasma were 15 and 7.0 µM (female), and 79 and 3.2 µM (male), respectively. Rat kidney slices prepared from normal SD rats were incubated with pooled plasma of female EHBRs for 2 hr, and the tissue samples were homogenized. MDCK II cells stably expressing OAT1 or 3 were incubated with pooled plasma of female (for GA) or male (for compound 1) EHBRs for 15 min, and the contents in the cells were extracted using ethanol. The concentrations of compound 1 and GA in the homogenates and the extracts were measured by LC-MS/MS. Data are plotted as mean ± S.E. (n = 3 for kidney slices of GA; n = 6 for kidney slices of compound 1; n = 6 for cell experiments). ^*P < 0.05 by Student’s t-test (A,B) or by one-way ANOVA (C,D).