Comparative uptake of grepafloxacin and ciprofloxacin by a human monocytic cell line, THP-1

Hara, Toshimasa; Takemura, Hiromu; Kanemitsu, Keiji; Yamamoto, Hiroyuki; Shimada, Jingoro

doi:10.1007/s101560070016

Cited by 12 publications

(12 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FQ accumulation differed between drugs: it was limited for CIP (K ϭ 1.5 Ϯ 0.1), intermediate for MXF (K ϭ 4.3 Ϯ 0.7), and quite large for GRX (K ϭ 25.2 Ϯ 0.9). These results are consistent with data in the literature, since K values of 3 for CIP and 16 for MXF were reported in experiments using J774 murine macrophages (30), 7 for CIP and 8 for MXF when using human macrophage cell line THP-1 cells (31), and 6.6 for CIP and 24.1 for GRX when using the same human macrophages from cell line THP-1 (32). Differences in apparent cell accumulation between these three FQs may be related to their lipophilicity, with the highest cell accumulation for GRX and the lowest for CIP, in agreement with log(D) values at physiological pH equal to 0.03, Ϫ0.28, and Ϫ0.93 for GRX, MFX, and CIP respectively (8).…”

Section: Discussionsupporting

confidence: 92%

Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

Gontijo

Brillault

Grégoire

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The aim of this study was to evaluate the biopharmaceutical characteristics of three fluoroquinolones (FQs), ciprofloxacin (CIP), moxifloxacin (MXF), and grepafloxacin (GRX), after delivery via a nebulized aerosol to rats. Bronchoalveolar lavages (BAL) were conducted 0.5, 2, 4, and 6 h after FQ intravenous administration and nebulized aerosol delivery to estimate epithelial lining fluid (ELF) drug concentrations. Plasma drug concentrations were also measured, and profiles of drug concentrations versus time after intravenous administration and nebulized aerosol delivery were virtually superimposable, attesting for rapid and complete systemic absorption of FQs. ELF drug concentrations were systematically higher than corresponding plasma drug concentrations, whatever the route of administration, and average ELF-to-unbound plasma drug concentration ratios post-distribution equilibrium did not change significantly between the ways of administration and were equal: 4.0 ؎ 5.3 for CIP, 12.6 ؎ 7.3 for MXF, and 19.1 ؎ 10.5 for GRX (means ؎ standard deviations). The impact of macrophage lysis on estimated ELF drug concentrations was significant for GRX but reduced for MXF and CIP; therefore, simultaneous pharmacokinetic modeling of plasma and ELF drug concentrations was only performed for the latter two drugs. The model was characterized by a fixed volume of ELF (V ELF ), passive diffusion clearance (Q ELF ), and active efflux clearance (CL out ) between plasma and ELF, indicating active efflux transport systems. In conclusion, this study demonstrates that ELF drug concentrations of these three FQs are several times higher than plasma drug concentrations, probably due to the presence of efflux transporters at the pulmonary barrier level, but no biopharmaceutical advantage of FQ nebulization was observed compared with intravenous administration.

show abstract

Section: Discussionsupporting

confidence: 92%

Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

Gontijo

Brillault

Grégoire

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…The data presented in this paper, together with those of previous publications (3,5,7,13), show that quinolones are accumulated by macrophages but to quite different extents. Many studies also report that quinolones accumulated by cells are active against intracellular bacteria sojourning in different subcellular compartments (see reference 4 for a recent review).…”

Section: Discussionsupporting

confidence: 73%

“…Early investigations had revealed that certain on May 12, 2018 by guest http://aac.asm.org/ quinolones are accumulated to some extent by macrophages even when these are maintained at 4°C (3,13) and that ciprofloxacin accumulation is enhanced in cells subjected to transient heat shock (9). This intriguing behavior was systematically reexamined here for all four quinolones studied.…”

Section: Kinetics Of Accumulation Of Quinolonesmentioning

confidence: 99%

“…Fluoroquinolones have long been known to accumulate in phagocytic cells (8), but quite significant differences among closely related derivatives have been observed (3,7,13) which have so far not received satisfactory explanation. One factor that can modulate antibiotic accumulation in eucaryotic cells is their differential recognition by active efflux transporters (see reference 28 and the references cited therein).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Influence of Efflux Transporters on the Accumulation and Efflux of Four Quinolones (Ciprofloxacin, Levofloxacin, Garenoxacin, and Moxifloxacin) in J774 Macrophages

Michot

Seral

Bambeke

et al. 2005

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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][2674][2675][2676][2677][2678][2679][2680][2681][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 14 C-labeled ciprofloxacin was increased by unlabeled ciprofloxacin and moxifloxacin, but moxifloxacin was two times less potent. Accumulation of moxifloxacin at 4°C was almost identical to that at 37°C, whereas that of ciprofloxacin was minimal (levofloxacin and garenoxacin showed intermediate behaviors). Cells subjected to thermal shock (56°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.Fluoroquinolones have long been known to accumulate in phagocytic cells (8), but quite significant differences among closely related derivatives have been observed (3, 7, 13) which have so far not received satisfactory explanation. One factor that can modulate antibiotic accumulation in eucaryotic cells is their differential recognition by active efflux transporters (see reference 28 and the references cited therein). Fluoroquinolones are recognized by several eucaryotic multidrug transporters, most notably by two main members of the ATP-binding cassette superfamily, namely the multidrug resistance-related proteins (MRP) and the P-glycoprotein (28). In J774 macrophages, norfloxacin has been shown to be subject to efflux by a probenecid-and gemfibrozil-inhibitable transporter (2), which has been tentatively identified as a member of the MRP family (16). In this context, we have now examined the accumulation and efflux of levofloxacin and moxifloxacin in J774 macrophages in comparison with ciprofloxacin. These quinolones were chosen on the basis of their increasingly lipophilic character and potential clinic...

show abstract

“…lung [29,30] , kidney [31] , macrophages [1,32] , monocytes [4][5][6][7][8][9]11] and PMNs [20,33] ), where they are intracellularly concentrated and alter bactericidal functions. Uptake of GPFX by an active transport system plateaus within the first 5 min of incubation [33] .…”

Section: Effects Of Grepafloxacinmentioning

confidence: 99%

Effects of Grepafloxacin on the Function of Human Polymorphonuclear Leukocytes and the Phosphorylation of p38 Mitogen-Activated Protein Kinase

Koshio

Ono²

2009

Chemotherapy

View full text Add to dashboard Cite

Background: Some new quinolones (NQs) modulate polymorphonuclear leukocyte (PMN) functions. We investigated these effects on PMN functions at concentrations <10 μg/ml. Methods: Chemotactic activity and the production of reactive oxygen species (ROS) were measured using a 48-well chemotaxis chamber and by luminol-dependent chemiluminescence (CL) activity, respectively. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was measured by Western blot using specific antibodies to its phosphorylation sites. Results: Grepafloxacin (GPFX) at concentrations >5 μg/ml increased the chemotactic activity and ROS production of PMNs after stimulation with N-formylmethionyl-leucyl-phenylalanine (fMLP), whereas prulifloxacin (PUFX) showed no effect. In contrast to PUFX, GPFX at concentrations >1 μg/ml stimulated the phosphorylation of p38 MAPK. Conclusions: GPFX enhanced the chemotactic activity and ROS production of PMNs after stimulation with fMLP at concentrations <10 μg/ml. These effects of GPFX on PMNs could be in part due to the enhancement of p38 MAPK phosphorylation.

show abstract

Comparative uptake of grepafloxacin and ciprofloxacin by a human monocytic cell line, THP-1

Cited by 12 publications

References 22 publications

Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

Influence of Efflux Transporters on the Accumulation and Efflux of Four Quinolones (Ciprofloxacin, Levofloxacin, Garenoxacin, and Moxifloxacin) in J774 Macrophages

Effects of Grepafloxacin on the Function of Human Polymorphonuclear Leukocytes and the Phosphorylation of p38 Mitogen-Activated Protein Kinase

Contact Info

Product

Resources

About