論文 - 詳細
| RRC ID | 41379 |
|---|---|
| 著者 | Naruhashi K, Tamai I, Inoue N, Muraoka H, Sai Y, Suzuki N, Tsuji A. |
| タイトル | Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein. |
| ジャーナル | J Pharm Pharmacol |
| Abstract |
Transport of quinolone antimicrobials and the contribution of the secretory transporter P-glycoprotein were studied in-vivo and 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. |
| 巻・号 | 53(5) |
| ページ | 699-709 |
| 公開日 | 2001-5-1 |
| DOI | 10.1211/0022357011775820 |
| PMID | 11370709 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B / pharmacology* ATP Binding Cassette Transporter, Subfamily B, Member 1 / pharmacology* ATP-Binding Cassette Transporters / pharmacology* Animals Anti-Infective Agents / pharmacokinetics* Biological Transport Caco-2 Cells Cell Line Fluoroquinolones Humans Intestinal Absorption Male Mice Rats Rats, Sprague-Dawley |
| IF | 2.571 |
| 引用数 | 46 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | LLC-GA5-CoL150(RCB0871) |