Carrier-mediated system for pefloxacin uptake in human monocytes

Mémin, Elisabeth; Panteix, G.; Revol, A

doi:10.1093/jac/40.2.263

Cited by 12 publications

(16 citation statements)

References 18 publications

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“…The extracellular Ca 2ϩ -induced decrease in levofloxacin uptake could be related to an alteration in the structural conformation of this drug (396). However, one active transport system (or possibly two) has been recognized recently for pefloxacin, ciprofloxacin, norfloxacin, and lomefloxacin (228,250,406). In particular, it was proposed that PMNs continuously transport ciprofloxacin via a transport pathway shared by adenine (406).…”

Section: Complex Game For Two or More Players With High Stakesmentioning

confidence: 99%

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

Labro¹

2000

Clinical Microbiology Reviews

150

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Section: Complex Game For Two or More Players With High Stakesmentioning

confidence: 99%

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

Labro¹

2000

Clinical Microbiology Reviews

150

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“…Although most data point to a passive mechanism, as has been postulated for many fluoroquinolones, others are typical of an active mechanism. In fact, a passive mechanism (2, 17), a carrier-mediated process (9), and an energy mechanism have been postulated for different fluoroquinolones (3,12,18,20).…”

mentioning

confidence: 99%

Intracellular Penetration and Activity of Gemifloxacin in Human Polymorphonuclear Leukocytes

Garcı́a

Pascual

Ballesta

et al. 2000

Antimicrob Agents Chemother

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The intracellular penetration and activity of gemifloxacin in human polymorphonuclear leukocytes (PMN) were evaluated. Gemifloxacin reached intracellular concentrations eight times higher than extracellular concentrations. The uptake was rapid, reversible, and nonsaturable and was affected by environmental temperature, cell viability, and membrane stimuli. At therapeutic extracellular concentrations, gemifloxacin showed intracellular activity against Staphylococcus aureus.Most fluoroquinolones are able to concentrate intracellularly in human phagocytic cells and remain active against facultatively and obligately intracellular pathogens, such as mycobacteria, Legionella spp., Streptococcus pneumoniae, and Staphylococcus aureus (16). Gemifloxacin is a new fluoroquinolone which displays more potent activity than sparfloxacin against gram-positive organisms and anaerobes (5,7,10). In addition, it shows excellent in vitro activity against other respiratory pathogens, such as Chlamydia pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae (1,19). The purpose of this study was to evaluate the uptake of gemifloxacin by human polymorphonuclear leukocytes (PMN). Also evaluated were the mechanisms involved in the penetration of this agent into the PMN and its intracellular activity against S. aureus.PMN uptake of radiolabeled gemifloxacin (64.5 Ci/mg; SB Pharmaceuticals, Harlow, United Kingdom) was determined by means of a velocity gradient centrifugation technique described by Klempner and Styrt (6). PMN were incubated in Hanks balanced salt solution containing different concentrations of gemifloxacin (0.1 to 25 g/ml). After different incubation periods at 37°C (1 to 60 min), cells were separated from the extracellular solution by centrifugation through a waterimpermeable silicone oil barrier. A 10-l aliquot of the extracellular medium and the entire cell pellet were placed in 3 ml of scintillation fluid (Ready Micro; Beckman Instruments, Inc., Fullerton, Calif.) and counted in a liquid scintillation counter (model LS 1801; Beckman). The accumulation rate of gemifloxacin was calculated and expressed as a cellular-to-extracellular-concentration ratio (C/E ratio) (11). The efflux of cellassociated gemifloxacin was also studied. All assays were performed in duplicate with PMN from four different donors. Data were expressed as means Ϯ standard deviations. Differences among groups were compared by variance analysis, used to assess statistical significance at a P value of Յ0.05.The kinetics of the uptake and efflux of gemifloxacin by PMN are shown in Fig. 1. The uptake of gemifloxacin by the PMN was rapid and high. At extracellular concentrations of 2 g/ml, the C/E ratios were higher than 7 after 20 min of incubation. This value is similar to those described for ciprofloxacin, ofloxacin, levofloxacin, and sparfloxacin (2, 13, 14) and slightly lower than those described for trovafloxacin and moxifloxacin (17, 18). Reversibility of binding was rapid for gemifloxacin, with 60% of the cell-associated drug being lost after 5...

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“…Fluoroquinolones utilize several different transporter systems to enter cells. 7 Ofloxacin has been shown to use aminoacid transporters to gain entry into neutrophils, whereas anion transporters are implicated in norfloxacin transport. Unfortunately, the mechanism for TVX and MBX is not known.…”

Section: Discussionmentioning

confidence: 99%

“…6 On the other hand, Mémin et al reported that pefloxacin was actively transported at 42°C in in vitro study. 7 It may be that quinolones can penetrate into cells passively in normal physical conditions, while some may be actively transported when the temperature or pH is modified. 7 TVX is able to concentrate inside phagocytic and nonphagocytic cells, attaining concentrations numerous times greater than those seen extracellularly.…”

Section: Introductionmentioning

confidence: 99%

“…7 It may be that quinolones can penetrate into cells passively in normal physical conditions, while some may be actively transported when the temperature or pH is modified. 7 TVX is able to concentrate inside phagocytic and nonphagocytic cells, attaining concentrations numerous times greater than those seen extracellularly. A study using radiolabeled TVX, with human polymorphonuclear leukocytes (PMNs) and human peritoneal macrophages, demonstrated that TVX at therapeutic extracellular concentrations reached intracellular concentrations in PMNs of 10-fold or more greater than extracellular levels.…”

Section: Introductionmentioning

confidence: 99%

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Feasibility of multiphoton microscopy-based quantification of antibiotic uptake into neutrophil granulocytes

et al. 2013

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Abstract. Antibiotic levels in livestock are usually evaluated through destructive analysis. Taking advantage of the fluorescent properties of marbofloxacin (MBX) and trovafloxacin (TVX), multiphoton microscopy (MPM) was evaluated as a minimally invasive and nondestructive method to determine the penetration of TVX and MBX into sheep neutrophils. Standard curves were measured with drug-only solutions and suggested that MBX was more suited for this type of analysis. The intracellular concentration of both TVX and MBX was higher than the extracellular concentration after incubating neutrophils for 30 min at concentrations ranging from 0.1 to 100 μg∕ml for both the drugs. The intracellular concentration of TVX increased with the extracellular concentration but was always greater than the extracellular concentration, suggesting active internalization. On the other hand, intracellular/extracellular ratio (I/E) peaked at 1.6-fold I/E for 1 μg∕ml and then gradually decreased with increased concentration to 1.2-fold I/E at 100 μg∕ml. For the first time, this study showed the use of MPM to quantify antibiotic uptake by sheep neutrophils and observed that both antibiotics were taken up by sheep neutrophils beyond extracellular levels. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Carrier-mediated system for pefloxacin uptake in human monocytes

Cited by 12 publications

References 18 publications

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

Intracellular Penetration and Activity of Gemifloxacin in Human Polymorphonuclear Leukocytes

Feasibility of multiphoton microscopy-based quantification of antibiotic uptake into neutrophil granulocytes

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