Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein
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- Kazumasa Naruhashi
- Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan
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- Ikumi Tamai
- Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan
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- Natsuko Inoue
- Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan
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- Hiromi Muraoka
- Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan
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- Yoshimichi Sai
- Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan
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- Nagao Suzuki
- Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan
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- Akira Tsuji
- Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan
抄録
<jats:title>Abstract</jats:title> <jats:p>Transport of quinolone antimicrobials and the contribution of the secretory transporter P-glycoprotein were studied in-vivoand in-vitro. In rat intestinal tissue (Ussing chambers method) and human Caco-2 cells (Transwell method), grepafloxacin showed secretory-directed transport. In both experimental systems, the secretory-directed transport was decreased by ciclosporin A, an inhibitor of P-glycoprotein, and probenecid, an inhibitor of anion transport systems. This suggested the contribution of P-glycoprotein and anion-sensitive transporter(s). The involvement of P-glycoprotein was investigated by using a P-glycoprotein over-expressing cell line, LLC-GA5-COL150, and P-glycoprotein-gene-deficient mice (mdr1a(—/—)/1b(—/—) mice). LLC-GA5-COL150 cells showed secretory-directed transport of grepafloxacin, while the parent cell line, LLC-PK1, did not. The secretory-directed transport of sparfloxacin and levofloxacin was also detected in LLC-GA5-COL150 cells. In the mdr1a(—/—)/1b(—/—) mice, the intestinal secretory clearance was smaller than that in wild-type mice after intravenous administration of grepafloxacin. Moreover, the absorption from an intestinal loop in mdr1a(—/—)/1b(—/—) mice was larger than that in wild-type mice. Accordingly, it appears that some quinolones are transported by secretory transporters, including P-glycoprotein. The involved transporters function in-vivo not only to transport grepafloxacin from blood to intestine but also to limit its intestinal absorption.</jats:p>
収録刊行物
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- Journal of Pharmacy and Pharmacology
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Journal of Pharmacy and Pharmacology 53 (5), 699-709, 2001-05
Oxford University Press (OUP)
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詳細情報 詳細情報について
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- CRID
- 1361418521136823552
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- NII論文ID
- 80012422265
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- ISSN
- 20427158
- 00223573
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- データソース種別
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