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

J Pharm Pharmacol. 2001 May;53(5):699-709. doi: 10.1211/0022357011775820.


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.

MeSH terms

  • 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


  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Anti-Infective Agents
  • Fluoroquinolones
  • multidrug resistance protein 3