ATP Binding Cassette Transporter, Subfamily B, Member 1
/ metabolism
ATP Binding Cassette Transporter, Subfamily G, Member 2
/ metabolism
Biological Transport
/ physiology
Cell Line
Epithelial Cells
/ metabolism
Fluoroquinolones
/ metabolism
Humans
Phosphatidylserines
/ metabolism
Phospholipids
/ metabolism
Pulmonary Surfactants
/ metabolism
Quinolones
/ metabolism
lascufloxacin
pulmonary distribution
quinolones
transporters
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
23
10
2018
accepted:
25
01
2019
pubmed:
6
2
2019
medline:
27
2
2020
entrez:
6
2
2019
Statut:
epublish
Résumé
The present study aimed to clarify the mechanism underlying the high distribution of lascufloxacin in epithelial lining fluid (ELF). Involvement of transporters was examined by transcellular transport across Calu-3 and transporter-overexpressing cells; the binding of lascufloxacin to ELF components was examined by an organic solvent-water partitioning system that employed pulmonary surfactant and phospholipids. Transcellular transport across the transporter-overexpressing cells indicated lascufloxacin to be a substrate of both P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); therefore, its transport across Calu-3 cells was inhibited by P-gp and BCRP inhibitors. However, permeability and efflux ratios of lascufloxacin were similar to those of the other quinolones with relatively low ELF distribution, indicating the existence of another mechanism for lascufloxacin distribution in ELF. Amongst pulmonary surfactants, which are a primary component of ELF, lascufloxacin preferentially bound to phosphatidylserine (PhS) from several phospholipids, and the binding was significantly greater than that for other quinolones. This binding was saturable with two apparent classes of binding sites and inhibited by some weakly basic drugs, indicating the presence of an ionic bond. In conclusion, the results of this study suggest that the binding of lascufloxacin to PhS in the pulmonary surfactant is the major mechanism of the high distribution of lascufloxacin in the ELF.
Identifiants
pubmed: 30718243
pii: AAC.02208-18
doi: 10.1128/AAC.02208-18
pmc: PMC6437485
pii:
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Fluoroquinolones
0
Phosphatidylserines
0
Phospholipids
0
Pulmonary Surfactants
0
Quinolones
0
lascufloxacin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
Références
Biochim Biophys Acta. 1998 Nov 19;1408(2-3):79-89
pubmed: 9813251
Antimicrob Agents Chemother. 2010 Feb;54(2):866-70
pubmed: 19933801
Antimicrob Agents Chemother. 2012 Jul;56(7):3873-8
pubmed: 22526307
J Lipid Res. 1991 Oct;32(10):1539-70
pubmed: 1797938
J Lipid Res. 1986 May;27(5):475-85
pubmed: 3755458
Int J Pharm. 2000 Nov 4;208(1-2):1-11
pubmed: 11064206
Pharm Res. 1990 Oct;7(10):1019-25
pubmed: 2281030
J Proteome Res. 2014 Sep 5;13(9):3919-29
pubmed: 25040188
Eur J Clin Pharmacol. 2012 Jan;68(1):39-53
pubmed: 21796376
Antimicrob Agents Chemother. 2005 Jun;49(6):2429-37
pubmed: 15917543
Antimicrob Agents Chemother. 2009 Apr;53(4):1457-62
pubmed: 19188390
Expert Opin Drug Metab Toxicol. 2011 Mar;7(3):353-64
pubmed: 21332386
Int J Pharm. 2010 Jan 15;384(1-2):32-8
pubmed: 19782742
Antimicrob Agents Chemother. 2013 Jun;57(6):2535-40
pubmed: 23507281
Antimicrob Agents Chemother. 2003 Aug;47(8):2538-44
pubmed: 12878516
Antimicrob Agents Chemother. 2008 Jan;52(1):24-36
pubmed: 17846133
J Infect Dis. 2005 Jun 15;191(12):2149-52
pubmed: 15898002
Antimicrob Agents Chemother. 2005 Jul;49(7):2642-7
pubmed: 15980331
J Pharmacol Exp Ther. 2001 Sep;298(3):1199-205
pubmed: 11504821
J Pharmacol Exp Ther. 2000 Oct;295(1):360-6
pubmed: 10992002
J Pharmacobiodyn. 1987 Mar;10(3):134-41
pubmed: 3625447
Respir Med. 1993 Nov;87(8):595-601
pubmed: 8290743
Antimicrob Agents Chemother. 2010 Jan;54(1):543-5
pubmed: 19822706
J Infect Dis. 2004 May 1;189(9):1590-7
pubmed: 15116294
Antimicrob Agents Chemother. 2018 Mar 27;62(4):
pubmed: 29339391
Chem Pharm Bull (Tokyo). 1983 Nov;31(11):4091-9
pubmed: 6689480
Respir Res. 2005 Jun 20;6:59
pubmed: 15967026
Drug Metab Dispos. 2002 Dec;30(12):1393-9
pubmed: 12433809
J Pharm Sci. 2001 May;90(5):647-58
pubmed: 11288109
Antimicrob Agents Chemother. 2017 May 24;61(6):
pubmed: 28320717
J Pharmacobiodyn. 1986 Oct;9(10):819-28
pubmed: 3820059
J Pharmacol Exp Ther. 2004 Aug;310(2):648-55
pubmed: 15131241
Eur J Pharmacol. 2001 Nov 23;431(3):297-303
pubmed: 11730721