Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P50583 (
asymmetrical
)
12,197
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The purpose of this study was to investigate the distribution of
Grepafloxacin
(
GPFX
), a new quinolone antimicrobial agent, in the lung epithelial lining fluid (ELF) and the alveolar macrophage (AM) in rats, which are potential infection sites in respiratory tract infections. We also aimed to clarify the mechanism governing the transferability of
GPFX
into the alveolus compartment from a kinetic point of view. The AUC ratios of ELF/plasma and AM/plasma after the oral administration of
GPFX
were 5.69 +/- 1.00 and 352 +/- 57, respectively, which were several-fold greater than those of ciprofloxacin (CPFX). Pharmacokinetic analyses of time profiles of
GPFX
concentrations in ELF and AM revealed that the influx clearance from plasma to ELF across the alveolar barrier is 5-fold greater than the efflux clearance from ELF. In addition, the permeability of
GPFX
across the cultured AM cell membrane was 7-fold and 11-fold greater than that of levofloxacin (LVFX) and CPFX, respectively. The extent of intracellular binding to AM cells (expressed as a constant (alpha)) was the greatest for
GPFX
, followed by CPFX and LVFX. There was a significant correlation between the alpha value and the partitioning to the immobilized artificial membrane (IAM) column, which consists of phospholipid residues covalently bound to silica. These results suggest that
GPFX
is highly distributed in ELF and AM, and that the high transferability of
GPFX
into ELF may be attributable to the existence of
asymmetrical
transport across the alveolar barrier. In addition, it was suggested that both rapid permeability across the AM cell membrane and avid binding to the membrane phospholipids may be responsible for the high accumulation of
GPFX
in AM.
...
PMID:Distribution characteristics of grepafloxacin, a fluoroquinolone antibiotic, in lung epithelial lining fluid and alveolar macrophage. 1561 51
