PT  - JOURNAL ARTICLE
AU  - Ito, Tatsuya
AU  - Yano, Ikuko
AU  - Tanaka, Kumiko
AU  - Inui, Ken-Ichi
TI  - Transport of Quinolone Antibacterial Drugs by Human P-Glycoprotein Expressed in a Kidney Epithelial Cell Line,  LLC-PK<sub>1</sub>
DP  - 1997 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 955--960
VI  - 282
IP  - 2
4099  - http://jpet.aspetjournals.org/content/282/2/955.short
4100  - http://jpet.aspetjournals.org/content/282/2/955.full
SO  - J Pharmacol Exp Ther1997 Aug 01; 282
AB  - The purpose of this study was to characterize the transport mechanisms involved in the renal tubular secretion of quinolones. The contribution of P-glycoprotein to the transport of quinolones was elucidated using a kidney epithelial cell line, LLC-PK1, and its transfectant derivative cell line, LLC-GA5-COL150, which expresses human P-glycoprotein on the apical membrane. The transcellular transport of levofloxacin, a quinolone antibacterial drug, from the basolateral to apical side was increased in LLC-GA5-COL150 compared with that in LLC-PK1 monolayers. The apparent Michaelis constant and maximum velocity values for the saturable transcellular transport of levofloxacin from the basolateral to apical side in LLC-GA5-COL 150 monolayers were 3.0 mM and 45 nmol/mg protein per 15 min, respectively. The increased basolateral-to-apical transport in LLC-GA5-COL150 monolayers was completely inhibited by cyclosporin A and quinidine to the level observed in LLC-PK1 monolayers. In addition, 3 mM levofloxacin inhibited the basolateral-to-apical transport of daunorubicin in LLC-GA5-COL150 monolayers. The basolateral-to-apical transport of another quinolone antibacterial drug, DU-6859a, in LLC-GA5-COL150 monolayers greatly exceeded than that in LLC-PK1monolayers, and was inhibited by levofloxacin. These findings suggest that quinolone antibacterial drugs are transported by P-glycoprotein, and that P-glycoprotein may contribute at least in part to the renal tubular secretion of quinolones. The American Society for Pharmacology and Experimental Therapeutics