Stereoselectivity of Ofloxacin Intestinal Transport in the Rat

Rabbaa, Lydia; Dautrey, Sophie; Colas-Linhart, N.; Carbon, C; Farinotti, Robert

doi:10.2165/00003495-199500492-00089

Cited by 7 publications

(6 citation statements)

References 4 publications

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“…Intestinal absorptive transport ( J a‐b ) for the fluoroquinolones enoxacin and ofloxacin has been characterized. Absorption of ofloxacin was highest at pH 7 (maximal pH of zwitterionic species) and decreased at pH 5 and pH 8 (Rabbaa et al , 1995). Prieto et al (1988), fitted a saturable Michaelis‐Menten process to the intestinal absorption of ofloxacin rather that a simple diffusion mechanism.…”

Section: Discussionmentioning

confidence: 98%

“…The intestine is also capable of the transport of lipophilic cationic drugs via the adenosine 5′‐triphosphate (ATP)‐driven efflux pump P‐glycoprotein, mediating transepithelial secretion of substrates such as vinblastine and digoxin (Hunter et al , 1993a, c; Cavet et al , 1996; Mayer et al , 1996). It has recently been suggested that P‐glycoprotein is involved in the transepithelial secretion of ofloxacin and ciprofloxacin in the rat (Rabbaa et al , 1995). ATP‐dependent extrusion of glutathione conjugates has also been documented in Caco‐2 intestinal epithelial cells; 1‐chloro‐2, 4‐dinitrobenzene (CDNB) is a substrate for glutathione‐S‐transferase, dinitrophenyl‐S‐glutathione (DNP‐SG) then being subject to ATP dependent secretion in Caco‐2 epithelia (Elferink et al , 1993).…”

Section: Introductionmentioning

confidence: 99%

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Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco‐2) cells

Cavet

West

Simmons

1997

British J Pharmacology

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Human intestinal epithelial Caco‐2 cells were used to investigate the mechanistic basis of transepithelial secretion of the fluoroquinolone antibiotic ciprofloxacin. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to competitive inhibition by sulphate, thiosulphate, oxalate, succinate and para‐amino hippurate, probenecid (10 mM), taurocholate (100 μM) or bromosulphophthalein (100 μM). Similarly tetraethylammonium and N‐′methylnicotinamide (10 mM) were without effect. Net secretion of ciprofloxacin was inhibited by the organic exchange inhibitor 4,4′‐diisothiocyanostilbene‐2‐2′‐disulphonic acid (DIDS, 400 μM). Net secretion of ciprofloxacin was partially inhibited by 100 μM verapamil, whilst net secretion of the P‐glycoprotein substrate vinblastine was totally abolished under these conditions. Ciprofloxacin secretion was unaltered after preincubation of cells with two anti‐P‐glycoprotein antibodies (UIC2 and MRK16), which both significantly reduced secretory vinblastine flux (measured in the same cell batch). Ciprofloxacin (3 mM) failed to inhibit vinblastine net secretion in Caco‐2 epithelia, and was not itself secreted by the P‐glycoprotein expressing and vinblastine secreting dog kidney cell line, MDCK. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to alterations of either cytosolic or medium pH, or dependent on the presence of medium Na+, Cl− or K+ in the bathing media. The substrate specificity of the ciprofloxacin secretory transport in Caco‐2 epithelia is distinct from both the renal organic anion and cation transport. A role for P‐glycoprotein in ciprofloxacin secretion may also be excluded. A novel transport mechanism, sensitive to both DIDS and verapamil mediates secretion of ciprofloxacin by human intestinal Caco‐2 epithelia. British Journal of Pharmacology (1997) 121, 1567–1578; doi:

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco‐2) cells

Cavet

West

Simmons

1997

British J Pharmacology

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“…Despite this low rate of biliary elimination, drug concentrations in the gut lumen are high following parenteral application, as demonstrated for ciprofloxacin, the first widely marketed fluoroquinolone ( Sorgel et al ., 1989 ). These findings suggested a trans ‐intestinal elimination, and a few years later, Rabbaa et al . (1995) hypothesized that permeability‐glycoprotein (P‐gp) might be involved in the trans‐epithelial secretion of ciprofloxacin as well as ofloxacin.…”

Section: Introductionmentioning

confidence: 85%

Danofloxacin‐mesylate is a substrate for ATP‐dependent efflux transporters

Schrickx

Fink‐Gremmels

2007

British J Pharmacology

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Background and purpose: Next to its broad antimicrobial spectrum, the therapeutic advantages of the fluoroquinolone antimicrobial drug Danofloxacin-Mesylate (DM) are attributed to its rapid distribution to the major target tissues such as lungs, intestines and the mammary gland in animals. Previous analyses revealed that effective drug concentrations are achieved also in luminal compartments of these organs, suggesting that active transport proteins facilitate excretion into the luminal space. Members of the ATP-Binding Cassette (ABC) superfamily, including P-gp, BCRP and MRP2 are known to be expressed in many tissue barriers and in cell-membranes facing luminal compartments. Hence we hypothesized that DM is a substrate for one of these efflux-transporters. Experimental approach: Confluent monolayers of Caco-2 cells, grown on microporous membranes in two-chamber devices were used. DM concentrations were measured by fluorimetric assay after HPLC of the culture media. Key results: DM transport across Caco-2 cells was asymmetric, with a rate of secretion exceeding that of absorption. The P-gp inhibitors PSC833 and GF120918 and the MRP-inhibitor MK571 partially decreased the secretion of DM and increased its absorption rate. The BCRP inhibitor, Ko143, decreased secretion only at a concentration of 1 mM. When DM was applied together with ciprofloxacin, secretion as well as absorption of DM decreased. Conclusions and Implications: DM is a substrate for the efflux transporters P-gp and MRP2, whereas the specific role of BCRP in DM transport needs further evaluation. These findings provide a mechanistic basis for the understanding of the pharmacokinetics of DM in healthy and diseased individuals.

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“…Several reports have been documented in enantioseparation of ofloxacin, including HPLC separation of diastereomers on an octadecylsilane RP column after derivatization [5], chiral separation by ligand exchange chromatography [6 -9], separation on a chiral stationary phase with BSA immobilized on silica gel [10], and CE [11].…”

Section: Introductionmentioning

confidence: 99%

Open tubular layer of S‐ofloxacin imprinted polymer fabricated in silica capillary for chiral CEC separation

Zaidi

Han

Kim

et al. 2009

J of Separation Science

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An open tubular molecule imprinted polymer (OT-MIP) capillary column has been prepared for chiral separation of ofloxacin enantiomers in CEC. The S-ofloxacin imprinted OT column was fabricated by thermally initiated non-covalent polymerization procedure inside a pretreated and silanized fused silica capillary. The template molecule was incorporated with methacrylic acid (MAA), ethylene glycol dimethacrylate (EDMA) and 4-styrenesulfonic acid (4-SSA) and dissolved in a porogen mixture of ACN/2-propanol (9:1). The separation efficiency of the 4-SSA MIP column was found quite better than that of the MIP column without 4-SSA. It has been demonstrated that our OT-MIP column can separate ofloxacin enantiomers with excellent chiral separation efficiency after tuning the various chromatographic conditions. The optimized chromatographic eluent was 85:15, v/v%, ACN/60 mM sodium acetate at pH 7. The separation efficiency and selectivity of chiral separation of this study were far better than those obtained by previous methods for chiral separation of R- and S-ofloxacin.

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Stereoselectivity of Ofloxacin Intestinal Transport in the Rat

Cited by 7 publications

References 4 publications

Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco‐2) cells

Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco‐2) cells

Danofloxacin‐mesylate is a substrate for ATP‐dependent efflux transporters

Open tubular layer of S‐ofloxacin imprinted polymer fabricated in silica capillary for chiral CEC separation

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