Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein.

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Naruhashi K, Tamai I, Inoue N, Muraoka H, Sai Y, Suzuki N, Tsuji A

Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein.

J Pharm Pharmacol. 2001 May;53(5):699-709.

PubMed ID

11370709 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Grepafloxacin	P-glycoprotein 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Sparfloxacin	P-glycoprotein 1	Protein	Humans	Unknown	Substrate	Details