Active Uptake of Ulifloxacin from Plasma to Lung That Controls Its Concentration in Epithelial Lining Fluid

Aoki, Makoto; Iguchi, Maki; Hayashi, Hiroyuki; Shibasaki, Shigeki; Kurosawa, Tohru; Hayashi, Masahiro

doi:10.1248/bpb.32.1095

Cited by 4 publications

(1 citation statement)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have suggested that active transporter systems in epithelial cells may be involved and may influence the secretion of these agents in the lung. [103,[143][144][145] On the other hand, technical issues associated with the collection of BAL samples and measurement of ELF concentrations have been raised as other potential explanations for these observations. [12,13,15] Some authors have provided rationales as to why these confounding variables may not explain the higher observed ELF concentrations.…”

Section: Discussionmentioning

confidence: 99%

Penetration of Anti-Infective Agents into Pulmonary Epithelial Lining Fluid

Rodvold

George

Yoo

2011

Clinical Pharmacokinetics

204

205

View full text Add to dashboard Cite

The exposure-response relationship of anti-infective agents at the site of infection is currently being re-examined. Epithelial lining fluid (ELF) has been suggested as the site (compartment) of antimicrobial activity against lung infections caused by extracellular pathogens. There have been an extensive number of studies conducted during the past 20 years to determine drug penetration into ELF and to compare plasma and ELF concentrations of anti-infective agents. The majority of these studies estimated ELF drug concentrations by the method of urea dilution and involved either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Antibacterial agents such as macrolides, ketolides, newer fluoroquinolones and oxazolidinones have ELF to plasma concentration ratios of >1. In comparison, β-lactams, aminoglycosides and glycopeptides have ELF to plasma concentration ratios of ≤1. Potential explanations (e.g. drug transporters, overestimation of the ELF volume, lysis of cells) for why these differences in ELF penetration occur among antibacterial classes need further investigation. The relationship between ELF concentrations and clinical outcomes has been under-studied. In vitro pharmacodynamic models, using simulated ELF and plasma concentrations, have been used to examine the eradication rates of resistant and susceptible pathogens and to explain why selected anti-infective agents (e.g. those with ELF to plasma concentration ratios of >1) are less likely to be associated with clinical treatment failures. Population pharmacokinetic modelling and Monte Carlo simulations have recently been used and permit ELF and plasma concentrations to be evaluated with regard to achievement of target attainment rates. These mathematical modelling techniques have also allowed further examination of drug doses and differences in the time courses of ELF and plasma concentrations as potential explanations for clinical and microbiological effects seen in clinical trials. Further studies are warranted in patients with lower respiratory tract infections to confirm and explore the relationships between ELF concentrations, clinical and microbiological outcomes, and pharmacodynamic parameters.

show abstract

Section: Discussionmentioning

confidence: 99%

Penetration of Anti-Infective Agents into Pulmonary Epithelial Lining Fluid

Rodvold

George

Yoo

2011

Clinical Pharmacokinetics

204

205

View full text Add to dashboard Cite

show abstract

Pharmacokinetic evaluation of tissue distribution of pirfenidone and its metabolites for idiopathic pulmonary fibrosis therapy

Togami

Kanehira

Tada

2015

Biopharm & Drug Disp

View full text Add to dashboard Cite

Pirfenidone is the first and only clinically used anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis (IPF). It was reported previously that pirfenidone metabolites (5-hydroxypirfenidone and 5-carboxypirfenidone) also have anti-fibrotic effects. The present study evaluated the distribution of pirfenidone and its metabolites in the lung, liver and kidney tissues in rats. The time course for the different concentrations of pirfenidone, 5-hydroxypirfenidone and 5-carboxypirfenidone in the lung tissue following oral administration (30 mg/kg) to rats was lower than that in plasma, and the area under the drug concentration-time curve (AUC) ratios of lung/plasma for pirfenidone, 5-hydroxypirfenidone and 5-carboxypirfenidone were 0.52, 0.40 and 0.61, respectively. In in vitro transport experiments, the basolateral-to-apical transport of pirfenidone and its metabolites through the model of lung epithelial cell (Calu-3) monolayers was not significantly different from their apical-to-basolateral transport. In binding experiments, the binding rate of these drugs to the lung tissue was lower than that to the plasma protein. These findings suggest that the low distribution of pirfenidone and its metabolites in the lungs was based on their low affinities with lung tissue and not the transport characteristics of lung epithelial cells. On the other hand, the AUC ratios of liver/plasma for pirfenidone and 5-carboxypirfenidone were 2.3 and 6.5 and the AUC ratios of kidney/plasma were 1.5 and 20, respectively. The binding rates to the liver and kidney tissues were higher than those to the plasma protein. These results suggest that high concentrations of these drugs were found in the liver and kidney tissues.

show abstract

Improved characterization of aminoglycoside penetration into human lung epithelial lining fluid via population pharmacokinetics

Shin,

Zhang,

Zhou

et al. 2024

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Aminoglycosides are important treatment options for serious lung infections, but modeling analyses to quantify their human lung epithelial lining fluid (ELF) penetration are lacking. We estimated the extent and rate of penetration for five aminoglycosides via population pharmacokinetics from eight published studies. The area under the curve in ELF vs plasma ranged from 50% to 100% and equilibration half-lives from 0.61 to 5.80 h, indicating extensive system hysteresis. Aminoglycoside ELF peak concentrations were blunted, but overall exposures were moderately high.

show abstract

Active Uptake of Ulifloxacin from Plasma to Lung That Controls Its Concentration in Epithelial Lining Fluid

Cited by 4 publications

References 44 publications

Penetration of Anti-Infective Agents into Pulmonary Epithelial Lining Fluid

Penetration of Anti-Infective Agents into Pulmonary Epithelial Lining Fluid

Pharmacokinetic evaluation of tissue distribution of pirfenidone and its metabolites for idiopathic pulmonary fibrosis therapy

Improved characterization of aminoglycoside penetration into human lung epithelial lining fluid via population pharmacokinetics

Contact Info

Product

Resources

About