Fluoroquinolone transport

S., Couet, W., In vitro and in vivo investigations on fluoroquinolones efFects of the P-glycoprotein efflux transporter on brain distribution of sparfloxadn, Eur. J. Pharm. Sci. 2000, 12, 85-93. 

Merino G, Alvarez Al, Pulido MM, Molina AJ, Schinkel AH, Prieto JG (2006) Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone... 

We then used this Caco-2 cell assay to categorize representative fluoroquinolone drug substance permeability [50], The drugs demonstrated some concentration-dependent permeability indicative of active drug transport. Based upon comparison to labetalol, ciprofloxacin was classified as a LP drug, whereas levofloxacin, lomefloxacin, and ofloxacin were classified as HP drugs, which matched their human in vivo bioavailabilities. All four fluoroquinolone drugs were subject to efflux transport (ciprofloxacin > lomefloxacin > rhodamine 123 > levofloxacin > ofloxacin). 

The permeability values of CNV97100, a fluoroquinolone derivative, were obtained in different segments of rat small intestine. The compound was in solution and the pH of the perfusion fluids in each segment were the same. The permeability was lower in the terminal segment of the small intestine in accordance with the higher expression level of P-gp. In order to confirm that a saturable carrier was present, experiments at different concentrations of the quinolone were performed in the ileum and also in the whole small intestine. In both cases a non-linear correlation between permeability and concentration was found where, at the higher concentrations, the permeability values were higher thanks to saturation of the secretion transporter. 

Altered transport Efflux Reduced Uptake Tetracycline, Fluoroquinolones Aminoglycosides, Chloramphenicol... 

Resistance to quinolones may develop during therapy via mutations in the bacterial chromosomal genes encoding DNA gyrase or topoisomerase IV or by active transport of the drug out of the bacteria. No quinolone-modifying or quinolone-inactivating activities have been identified in bacferia. Resistance has increased after the introduction of fluoroquinolones. 

Certain antimicrobial dmgs are actively transported into infection sites. The active transport of fluoroquinolones and tetracyclines by gingival fibroblasts into gingival fluid is an example. ... 

Esrafih A, Yamini Y, Ghambarian M, Shariati S, Moradi M. Measurement of fluoroquinolone antibiotics from human plasma using hollow fiber liquid-phase microextraction based on carrier mediated transport. J Liq Chromatogr Rel Technol 2012 35 2040-2047. 

Neyfakh AA, Borsch CM, Kaatz GW (1993) Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a mirltidrug efflux transporter. Antimicrob Agents Chemother... 

The difference in activity for R- and -enantiomers of 7-(3-methylpiperazin-l-yl)quinolones, obtained from the corresponding (R)- and (5)-f-butyl-2-methylpiperazin-l-carboxylates, proved to be in the range from 2 to 64 folds in 52 % of cases [95]. In order to improve transport through biological membranes the piperazine moiety in norfloxacin was modified considerably and compound 26 was obtained [96]. To clarify the mechanism of antibacterial action of fluoroquinolones at the cellular level, two regioisomeric citrate-functionalized derivatives of ciprofloxacin 27a,b [97] (Scheme 14) have been obtained and studied. 

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