Fluoroquinolone Efflux Mediated by ABC Transporters

Alvarez, Ana I.; Pérez, Marcela Mastachi; Prieto, J. E.; Molina, A.; Real, Rebeca; Merino, Gracia

doi:10.1002/jps.21233

Cited by 74 publications

(64 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In has been reported in the literature that the tissue distribution of fluoroquinolones is influenced by efflux transporters (8,22,36). In the present work, we evaluated the distribution kinetics of LEV in plasma, lung, and prostate in the presence and absence of TAR in order to evaluate the impact of the efflux transporter P-gp (TAR group) on free interstitial drug concentrations.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration

Zimmermann

Laureano

Santos

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration

Zimmermann

Laureano

Santos

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…As has been recently highlighted, many fluoroquinolones are subject to ATP-binding cassette (ABC) transporter-mediated efflux (Alvarez et al, 2008). In a previous study, Griffiths et al (1993) demonstrated saturable ATP-dependent secretory transport in human intestinal Caco-2 cells with a number of fluoroquinolones sharing a common secretory pathway (Griffiths et al, 1993(Griffiths et al, , 1994.…”

Section: Introductionmentioning

confidence: 99%

Intestinal Ciprofloxacin Efflux: The Role of Breast Cancer Resistance Protein (ABCG2)

Haslam¹,

Wright²,

O’Reilly³

et al. 2011

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Intestinal secretory movement of the fluoroquinolone antibiotic, ciprofloxacin, may limit its oral bioavailability. Active ATP-binding cassette ( , and verapamil as ABC-selective inhibitors. In addition, the regional variation in secretory capacity was investigated using male Han Wistar rat intestine mounted in Ussing chambers, and the first indicative measurements of ciprofloxacin transport by ex vivo human jejunum were made. Active, Ko143-sensitive ciprofloxacin secretion was observed in bcrp1-MDCKII cell layers, but in low-passage (BCRP-expressing) Caco-2 cell layers only a 54% fraction was Ko143-sensitive. Ciprofloxacin accumulation was lower in MRP4-HEK293 cells than in the parent line, indicating that ciprofloxacin is also a substrate for this transporter. Ciprofloxacin secretion by Caco-2 cell layers was not inhibited by MK571. Secretory flux showed marked regional variability in the rat intestine, increasing from the duodenum to peak in the ileum. Ciprofloxacin secretion was present in human jejunum and was reduced by Ko143 but showed marked interindividual variability. Ciprofloxacin is a substrate for human and rodent BCRP. An additional pathway for ciprofloxacin secretion exists in Caco-2 cells, which is unlikely to be MRP(4)-mediated. BCRP is likely to be the dominant transport mechanism for ciprofloxacin efflux in both rat and human jejunum.

show abstract

“…Fluoroquinolones (FQs) have been shown to be substrates of efflux transport systems, including P-glycoprotein (P-gp), in various tissues and cell lines (1). We have recently shown that P-gp is expressed in Calu-3 lung epithelial cells and that it is responsible for an active efflux transport of moxifloxacin (MXF) as a representative FQ (2).…”

mentioning

confidence: 99%

Relative Contributions of Active Mediated Transport and Passive Diffusion of Fluoroquinolones with Various Lipophilicities in a Calu-3 Lung Epithelial Cell Model

Brillault

Castro

Couet

2010

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The transport characteristics of six fluoroquinolones (FQs) with various lipophilicities were compared in a Calu-3 cell model. For each FQ, an active polarized transport was observed in the direction of the apical side. However, the apparent permeability of FQs resulted from active transport and passive diffusion that were highly variable between compounds and mainly governed by lipophilicity. Therefore, active transport was predominant for compounds with relatively low lipophilicity but minor for FQs with higher lipophilicity.Fluoroquinolones (FQs) have been shown to be substrates of efflux transport systems, including P-glycoprotein (P-gp), in various tissues and cell lines (1). We have recently shown that P-gp is expressed in Calu-3 lung epithelial cells and that it is responsible for an active efflux transport of moxifloxacin (MXF) as a representative FQ (2). The objective of this new study was to compare the diffusion characteristics of several FQs with various lipophilicities, differentiating between passive diffusion and active transport, and to determine their relative contributions to the overall diffusion through Calu-3 cells.Ciprofloxacin (CIP) hydrochloride and moxifloxacin (MXF) hydrochloride were kindly supplied by Bayer Healthcare (Leverkusen, Germany); grepafloxacin (GRX) hydrochlorate was supplied by Otsuka Pharmaceutical Co. (Tokyo, Japan); and PSC-833 was supplied by Novartis (Basel, Switzerland). Commercial solutions of levofloxacin (LVX) and pefloxacin (PFX) from, respectively, Sanofi Aventis (Paris, France) and Rhône-Poulenc-Rorer (Antony, France) were used. Norfloxacin (NOR) was purchased from Sigma-Aldrich. Other chemicals and reagents had the same origins as previously described (2). Calu-3 cell culture, transport, and inhibition studies as well as tight junction integrity control were done as previously described (2), with FQ concentrations set at 50 M, corresponding to a third of the apparent K m for MXF transport (2), and chosen to limit the risk of efflux transporter saturation. FQ partition coefficients between octanol and pH 7.4 buffered solution (log D) were taken from the literature: NOR, Ϫ1.16, and CIP, Ϫ0.93 (10); LVX, Ϫ0.41, and GRX, 0.03 (11); MXF, Ϫ0.28 (5); and PFX, 0.25 (6). FQs were assayed by highperformance liquid chromatography with fluorescence detection using the same method as for MXF (2), except that excitatory and emission wavelengths were set at 285 and 490 nm, respectively, for MXF and LVX and at 285 and 444 nm, respectively, for GRX, PFX, CIP, and NOR and that the flow rate was 0.5 ml/min. The precisions intra-and interday for FQs were satisfactory, with CV values between 0.3 and 6.7%. Apparent permeability (P app ) values were obtained according to the following equation: P app ϭ Q/(T ϫ A ϫ C 0 ), where Q is the amount of drug in g that appeared in the acceptor compartment, T is the incubation time of 60 min, A is the semipermeable membrane surface area of 4.67 cm 2 , and C 0 is the initial concentration of FQ in the donor compartment in g/cm Ϫ3 . The efflux r...

show abstract

Fluoroquinolone Efflux Mediated by ABC Transporters

Cited by 74 publications

References 91 publications

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration

Simultaneous Semimechanistic Population Analyses of Levofloxacin in Plasma, Lung, and Prostate To Describe the Influence of Efflux Transporters on Drug Distribution following Intravenous and Intratracheal Administration

Intestinal Ciprofloxacin Efflux: The Role of Breast Cancer Resistance Protein (ABCG2)

Relative Contributions of Active Mediated Transport and Passive Diffusion of Fluoroquinolones with Various Lipophilicities in a Calu-3 Lung Epithelial Cell Model

Contact Info

Product

Resources

About