1: Antimicrob Agents Chemother. 2005 Jun;49(6):2429-37. 

Influence of efflux transporters on the accumulation and efflux of four
quinolones (ciprofloxacin, levofloxacin, garenoxacin, and moxifloxacin) in J774

Michot JM, Seral C, Van Bambeke F, Mingeot-Leclercq MP, Tulkens PM.

Unite de Pharmacologie Cellulaire et Moleculaire, Universite catholique de
Louvain, UCL 73.70 avenue E. Mounier 73, B-1200 Brussels, Belgium.

Ciprofloxacin is subject to efflux from J774 macrophages through a multidrug
resistance-related protein-like transporter (J. M. Michot, F. Van Bambeke, M. P.
Mingeot-Leclercq, and P. M. Tulkens, Antimicrob. Agents Chemother. 48:2673-2682,
2004). Here, we compare ciprofloxacin to levofloxacin, garenoxacin, and
moxifloxacin for transport. At 4 mg/liter, an apparent steady state in
accumulation was reached after 30 to 60 min for all quinolones but to quite
different levels (approximately 3, 5, 10, and 16 fold). Accumulation of
ciprofloxacin was increased (to about 16 to 20 fold) by ATP depletion, increase
in extracellular concentration, and the addition of probenecid, gemfibrozil, or
MK571 (but not verapamil or GF120918). These treatments did not affect the
accumulation of moxifloxacin. Levofloxacin and garenoxacin showed an
intermediate behavior. Efflux of ciprofloxacin was slowed down by probenecid
(half-life, 7.2 versus 1.6 min). Moxifloxacin efflux was faster and unaffected
by probenecid (half-lifes, 0.27 versus 0.33 min). Efflux of levofloxacin and
garenoxacin was modestly decreased by probenecid (1.5 and 2.1 fold).
Accumulation of 14C-labeled ciprofloxacin was increased by unlabeled
ciprofloxacin and moxifloxacin, but moxifloxacin was two times less potent.
Accumulation of moxifloxacin at 4 degrees C was almost identical to that at 37
degrees C, whereas that of ciprofloxacin was minimal (levofloxacin and
garenoxacin showed intermediate behaviors). Cells subjected to thermal shock (56
degrees C; 10 min) accumulated all quinolones at a similar level (16 to 23
fold). We conclude that moxifloxacin is apparently not subject to efflux from
J774 macrophages, even though it can interact with the ciprofloxacin
transporter. Levofloxacin and garenoxacin are partially effluxed. Data suggest
that efflux plays an important role in the differential accumulation of
quinolones by J774 macrophages.

PMID: 15917543 [PubMed - indexed for MEDLINE]