Transepithelial transport of levofloxacin in the isolated perfused rat kidney.
OBJECTIVE
The transepithelial transport of levofloxacin was evaluated in the isolated perfused kidney to investigate its renal secretory mechanisms.


METHODS
Levofloxacin was instantaneously administered into the renal artery together with inulin and Evans blue-labeled albumin, and the single-pass dilution curves of the renal venous and urinary outflow were determined in the absence or presence of various compounds. Kinetic parameters were computed based on non-compartment moment analysis.


RESULTS
The ratio of fractional excretion to filtration fraction (FE/FF) for levofloxacin was 2.99 +/- 0.18, indicating the involvement of tubular secretion. In the presence of cimetidine and quinolones, the FE/FF of levofloxacin was significantly decreased and the transepithelial mean transit time (Tcell) of levofloxacin was prolonged. The Tcell showed a negative correlation with renal secretion of levofloxacin, while the volume of distribution of levofloxacin showed no correlation.


CONCLUSIONS
Transport on the brush-border membrane plays a determining step in the renal secretion of levofloxacin, and cimetidine and quinolones interact with levofloxacin transport on the brush-border membrane.
Ito
T
T
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Yano
I
I
Hashimoto
Y
Y
Inui
K
K
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D000892:Anti-Infective Agents, Urinary / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes; D002927:Cimetidine / Q000494:pharmacology; D004396:Coloring Agents / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D005070:Evans Blue / Q000493:pharmacokinetics; D024841:Fluoroquinolones; D066298:In Vitro Techniques; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D064704:Levofloxacin; D008297:Male; D015242:Ofloxacin / Q000493:pharmacokinetics*; D010477:Perfusion; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014556:Urine; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D000890:Anti-Infective Agents; D000892:Anti-Infective Agents, Urinary; D002250:Carbon Radioisotopes; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D010879:Piperazines; D005070:Evans Blue; D019789:Tetraethylammonium; D064704:Levofloxacin; D002927:Cimetidine; D007444:Inulin; D015242:Ofloxacin; C075375:grepafloxacin; D010130:p-Aminohippuric Acid