Airway Epithelial Lining Fluid and Plasma Pharmacokinetics of Inhaled Fluticasone Propionate and Salmeterol Xinafoate in Mechanically Ventilated Pigs

2020 ◽  
Author(s):  
Pär Ewing ◽  
Steven Oag ◽  
Anders Lundqvist ◽  
Stina Stomilovic ◽  
Ida Stellert ◽  
...  
Keyword(s):  
Fluticasone Propionate ◽  
Epithelial Lining ◽  
Airway Epithelial ◽  
Epithelial Lining Fluid ◽  
Mechanically Ventilated ◽  
Salmeterol Xinafoate ◽  
Plasma Pharmacokinetics

Pharmacokinetics of intravenous peramivir in the airway epithelial lining fluid of healthy volunteers

2016 ◽  
Vol 21 (7) ◽  
pp. 621-625 ◽  
Author(s):  
Yohei Funatsu ◽  
Sadatomo Tasaka ◽  
Takahiro Asami ◽  
Ho Namkoong ◽  
Hiroshi Fujiwara ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Epithelial Lining ◽  
Airway Epithelial ◽  
Epithelial Lining Fluid

Release of Beryllium Into Artificial Airway Epithelial Lining Fluid

2012 ◽  
Vol 67 (4) ◽  
pp. 219-228 ◽  
Author(s):  
Aleksandr B. Stefaniak ◽  
M. Abbas Virji ◽  
Gregory A. Day
Keyword(s):  
Epithelial Lining ◽  
Airway Epithelial ◽  
Epithelial Lining Fluid ◽  
Artificial Airway

scholarly journals Lung Pharmacokinetics of Tobramycin by Intravenous and Nebulized Dosing in a Mechanically Ventilated Healthy Ovine Model

2019 ◽  
Vol 131 (2) ◽  
pp. 344-355 ◽  
Author(s):  
Jayesh A. Dhanani ◽  
Sara Diab ◽  
Jivesh Chaudhary ◽  
Jeremy Cohen ◽  
Suzanne L. Parker ◽  
...  
Keyword(s):  
Interstitial Fluid ◽  
Jugular Vein ◽  
Interstitial Space ◽  
Interquartile Range ◽  
Pharmacokinetic Studies ◽  
Ventilator Associated Pneumonia ◽  
Epithelial Lining ◽  
Ovine Model ◽  
Epithelial Lining Fluid ◽  
Mechanically Ventilated

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Nebulized antibiotics may be used to treat ventilator-associated pneumonia. In previous pharmacokinetic studies, lung interstitial space fluid concentrations have never been reported. The aim of the study was to compare intravenous and nebulized tobramycin concentrations in the lung interstitial space fluid, epithelial lining fluid, and plasma in mechanically ventilated sheep with healthy lungs. Methods Ten anesthetized and mechanically ventilated healthy ewes underwent surgical insertion of microdialysis catheters in upper and lower lobes of both lungs and the jugular vein. Five ewes were given intravenous tobramycin 400 mg, and five were given nebulized tobramycin 400 mg. Microdialysis samples were collected every 20 min for 8 h. Bronchoalveolar lavage was performed at 1 and 6 h. Results The peak lung interstitial space fluid concentrations were lower with intravenous tobramycin 20.2 mg/l (interquartile range, 12 mg/l, 26.2 mg/l) versus the nebulized route 48.3 mg/l (interquartile range, 8.7 mg/l, 513 mg/l), P = 0.002. For nebulized tobramycin, the median epithelial lining fluid concentrations were higher than the interstitial space fluid concentrations at 1 h (1,637; interquartile range, 650, 1,781, vs. 16 mg/l, interquartile range, 7, 86, P < 0.001) and 6 h (48, interquartile range, 17, 93, vs. 4 mg/l, interquartile range, 2, 9, P < 0.001). For intravenous tobramycin, the median epithelial lining fluid concentrations were lower than the interstitial space fluid concentrations at 1 h (0.19, interquartile range, 0.11, 0.31, vs. 18.5 mg/l, interquartile range, 9.8, 23.4, P < 0.001) and 6 h (0.34, interquartile range, 0.2, 0.48, vs. 3.2 mg/l, interquartile range, 0.9, 4.4, P < 0.001). Conclusions Compared with intravenous tobramycin, nebulized tobramycin achieved higher lung interstitial fluid and epithelial lining fluid concentrations without increasing systemic concentrations.

Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin.

1996 ◽  
Vol 40 (10) ◽  
pp. 2375-2379 ◽  
Author(s):  
K B Patel ◽  
D Xuan ◽  
P R Tessier ◽  
J H Russomanno ◽  
R Quintiliani ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Tissue Concentration ◽  
Epithelial Lining ◽  
Assay Sensitivity ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Time Points ◽  
Plasma Pharmacokinetics ◽  
Absolute Concentrations

The bronchopulmonary and plasma pharmacokinetics of clarithromycin (CLA; 500 mg given twice daily for nine doses) or azithromycin (AZ; 500 mg for the first dose and then 250 mg once daily for four doses) were assessed in 41 healthy nonsmokers. Bronchoalveolar lavage was performed at 4, 8, 12, or 24 h after administration of the last dose. The concentrations (mean +/- standard deviation) of CLA, 14-hydroxyclarithromycin, and AZ were measured in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) cells by high-performance liquid chromatography assay. The concentrations of CLA achieved in ELF were 34.02 +/- 5.16 micrograms/ml at 4 h, 20.63 +/- 4.49 micrograms/ml at 8 h, 23.01 +/- 11.9 micrograms/ml at 12 h, and 4.17 +/- 0.29 microgram/ml at 24 h, whereas at the same time points AZ concentrations remained below the limit of assay sensitivity (0.01 microgram/ml) for all but two subjects. The concentrations of CLA in the AM cells were significantly higher than those of AZ at 8 h (703 +/- 235 and 388 +/- 53 micrograms/ml, respectively). However, the ratio of the concentration in AM cells/concentration in plasma was significantly higher for AZ than for CLA for all time points because of the lower concentration of AZ in plasma. These results indicate that while AZ has higher tissue concentration to plasma ratios, as shown by other investigators, the absolute concentrations of CLA in AM cells and ELF are higher for up to 8 and 12 h, respectively, after administration of the last dose.

scholarly journals Pharmacodynamics of Moxifloxacin and Levofloxacin at Simulated Epithelial Lining Fluid Drug Concentrations against Streptococcus pneumoniae

2004 ◽  
Vol 48 (4) ◽  
pp. 1215-1221 ◽  
Author(s):  
Naomi R. Florea ◽  
Pamela R. Tessier ◽  
Cuilian Zhang ◽  
Charles H. Nightingale ◽  
David P. Nicolau
Keyword(s):  
Streptococcus Pneumoniae ◽  
Fluoroquinolone Resistance ◽  
Epithelial Lining ◽  
Time Curve ◽  
Bacterial Killing ◽  
Epithelial Lining Fluid ◽  
Log Reduction ◽  
Development Of Resistance ◽  
Drug Concentrations

ABSTRACT Recent clinical failures associated with levofloxacin treatment for Streptococcus pneumoniae infections and growing evidence of frequent mutations in the isolate population have led to increased concerns regarding fluoroquinolone resistance. Our objective was to characterize the efficacies of levofloxacin and moxifloxacin against various genotypes of S. pneumoniae after simulated bronchopulmonary exposures. An in vitro model was used to simulate a levofloxacin concentration of 500 mg and a moxifloxacin concentration of 400 mg, which were previously determined to be the concentrations in the epithelial lining fluid of older adults receiving once-daily dosing. The effects of the drugs were tested against six S. pneumoniae containing various mutations. Bacterial density and resistance were quantitatively assessed over 48 h. The S. pneumoniae isolate with no mutation displayed a 4-log reduction in CFU after treatment with both agents and did not develop resistance. Isolates containing the parC or parE mutation or both mutations regrew and developed resistance when they were exposed to levofloxacin, despite an unbound area under the concentration-time curve (AUC):MIC ratio of ∼100. When the isolate containing the parC and gyrA mutations was exposed to levofloxacin, there was a half-log reduction in the number of CFU compared to that for the control, but the isolate subsequently regrew. Likewise, levofloxacin did not kill the isolate containing the parC, gyrA, and parE mutations. Moxifloxacin sustained the killing of all bacterial isolates tested without the development of resistance. Levofloxacin did not sustain bacterial killing and did not prevent the emergence of further resistance in mutants with the parC or parE mutation or both mutations, even though an unbound AUC:MIC ratio for exposure well above the breakpoint of 30 to 40 established in the literature for S. pneumoniae was maintained. Moxifloxacin was effective against all isolates tested, despite the presence of isolates with two- and three-step mutations, for which the MICs were increased.

scholarly journals Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 5. Oseltamivir Carboxylate

2016 ◽  
Vol 60 (8) ◽  
pp. 5085-5087 ◽  
Author(s):  
Danilo Cesar Galindo Bedor ◽  
Sandrine Marchand ◽  
Isabelle Lamarche ◽  
Julian Laroche ◽  
Davi Pereira de Santana ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Area Under The Curve ◽  
Pulmonary Delivery ◽  
Epithelial Lining ◽  
Oseltamivir Carboxylate ◽  
Epithelial Lining Fluid

ABSTRACTThe aim of this study was to determine the biopharmaceutical characteristics of oseltamivir carboxylate (OC) after pulmonary delivery. After OC bolus and intratracheal nebulization (NEB) in rats, blood was collected and bronchoalveolar lavages (BALs) were performed. Epithelial lining fluid (ELF) concentrations were estimated from BAL fluid. The area under the curve (AUC) ratio for ELF to plasma was 842 times higher after NEB than after intravenous (i.v.) administration, indicating that OC nebulization offers a biopharmaceutical advantage over i.v. administration.

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