Distribution characteristics of levofloxacin and grepafloxacin in rat kidney.
OBJECTIVE
To elucidate the renal distribution of quinolones, we examined the uptake of levofloxacin and grepafloxacin in vivo and in rat renal cortical slices.


METHODS
The plasma and various tissue concentrations of levofloxacin and grepafloxacin were measured after a bolus injection in rats, and tissue uptake clearance was calculated. Transport characteristics of quinolones in rat renal cortical slices were evaluated.


RESULTS
The tissue distribution of levofloxacin and grepafloxacin in the kidney was greater than in any other tissue, and the tissue uptake clearances of levofloxacin and grepafloxacin in the kidney cortex were 1.2 and 4.6 ml/min/g tissue, respectively. The uptake of levofloxacin and grepafloxacin in rat renal cortical slices was concentrative, as indicated by slice/medium ratios of 2.3 and 9.6 at 60 min, respectively. The uptake of levofloxacin and grepafloxacin in rat renal cortical slices showed saturation, and was significantly inhibited in the presence of quinidine (p<.05), but not of tetraethylammonium or p-aminohippurate.


CONCLUSIONS
Renal distribution of levofloxacin and grepafloxacin may be mediated by a specific transport system for quinolones, distinct from the organic cation and organic anion transport systems in the kidney.
Ito
T
T
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Yano
I
I
Masuda
S
S
Hashimoto
Y
Y
Inui
K
K
D000818:Animals; D000890:Anti-Infective Agents / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism*; D007700:Kinetics; D064704:Levofloxacin; D008297:Male; D015242:Ofloxacin / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014018:Tissue Distribution; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D000890:Anti-Infective Agents; D002250:Carbon Radioisotopes; D024841:Fluoroquinolones; D010879:Piperazines; D019789:Tetraethylammonium; D064704:Levofloxacin; D002927:Cimetidine; D015242:Ofloxacin; C075375:grepafloxacin; D010130:p-Aminohippuric Acid