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Uptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2

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Abstract

Purpose

The aim of this study was to investigate the transport mechanisms of transporters that contribute to the intestinal uptake of 7-ethyl-10-hydroxycamptothecin (SN-38).

Methods

Human intestinal epithelial Caco-2 cells were used to investigate the mechanistic basis of transepithelial uptake of SN-38. We investigated the characteristics of SN-38 uptake into Caco-2 cells. The effects of baicalin and sulfobromophthalein (BSP) on the uptake of SN-38 by Caco-2 cells were examined.

Results

Uptake of SN-38 was significantly reduced at 4°C. Baicalin inhibited the uptake of SN-38 in a concentration-dependent manner. BSP significantly reduced the uptake of SN-38. However, probenecid, pravastatin and grepafloxacin did not affect the uptake of SN-38.

Conclusions

The results suggest that a specific transport system mediates the uptake of SN-38 across the apical membrane in Caco-2 cells.

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Acknowledgements

We thank Dr. S. Miyauchi for his advice on the experimental technique. This work was supported in part by grants from the Akiyama Foundation and the Japan Research Foundation for Clinical Pharmacology.

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Authors and Affiliations

  1. Department of Pharmacy, Sapporo Social Insurance General Hospital, Chuo 2-jo, 6-chome, Atsubetsu-ku, Sapporo, 004-8618, Japan

    Tatsuya Itoh & Isao Takemoto

  2. Department of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo, 060-0812, Japan

    Shirou Itagaki, Yoshinobu Sumi, Takeshi Hirano & Ken Iseki

Authors
  1. Tatsuya Itoh
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  2. Shirou Itagaki
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  3. Yoshinobu Sumi
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  4. Takeshi Hirano
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  5. Isao Takemoto
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  6. Ken Iseki
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Correspondence to Ken Iseki.

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Itoh, T., Itagaki, S., Sumi, Y. et al. Uptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2. Cancer Chemother Pharmacol 55, 420–424 (2005). https://doi.org/10.1007/s00280-004-0937-4

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  • DOI: https://doi.org/10.1007/s00280-004-0937-4

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