scholarly journals Concentrations of single-dose meropenem (1 g iv) in bronchoalveolar lavage and epithelial lining fluid

2000 ◽  
Vol 46 (2) ◽  
pp. 319-322 ◽  
Author(s):  
B. Allegranzi
Keyword(s):  
Single Dose ◽  
Bronchoalveolar Lavage ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid

scholarly journals Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects.

1996 ◽  
Vol 40 (7) ◽  
pp. 1617-1622 ◽  
Author(s):  
J E Conte ◽  
J Golden ◽  
S Duncan ◽  
E McKenna ◽  
E Lin ◽  
...  
Keyword(s):  
Single Dose ◽  
Bronchoalveolar Lavage ◽  
Peak Concentration ◽  
Area Under The Curve ◽  
Lavage Fluid ◽  
Diffusion Method ◽  
Alveolar Cells ◽  
Epithelial Lining Fluid ◽  
Drug Concentrations ◽  
Oral Doses

The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithormycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four subjects each, the subjects underwent bronchoscopy and bronchoalveolar lavage at timed intervals following drug administration. Drug concentrations, including those of 14-hydroxyclarithromycin (14H), were determined in serum, bronchoalveolar lavage fluid, and alveolar cells (ACs) by high-pressure liquid chromatography. Concentrations in epithelial lining fluid (ELF) were calculated by the urea diffusion method. The maximum observed concentrations (mean +/- standard deviation) of azithromycin, clarithromycin, 14H, ciprofloxacin, and cefuroxime in serum were 0.13 +/- 0.07, 1.0 +/- 0.6, 0.60 +/- 0.41, 0.95 +/- 0.32, and 1.1 +/- 0.3 microgram/ml, respectively (all at 6 h). None of the antibiotics except clarithromycin (39.6 +/- 41.1 micrograms/ml) was detectable in ELF at the 6-h bronchoscopy. The movement into and persistence in cells was different for azithromycin and clarithromycin. In ACs azithromycin was not detectable at 6 h, reached its highest concentration at 120 h, and exhibited the greatest area under the curve (7,403 micrograms.hr ml-1). The peak concentration of clarithromycin (181 +/- 94.1 micrograms/ml) was greater and occurred earlier (6 h), but the area under the curve (2,006 micrograms.hr ml-1) was less than that observed for azithromycin. 14H was detectable in ACs at 6 h (40.3 +/- 5.2 micrograms/ml) and 12 h (32.8 +/- 57.2 micrograms/ml). The peak concentration of ciprofloxacin occurred at 6 h (4.3 +/- 5.2 micrograms/ml), and the area under the curve was 35.0 micrograms.hr ml-1. The data indicate that after the administration of a single dose, azithromycin, clarithromycin, and ciprofloxacin penetrated into ACs in therapeutic concentrations and that only clarithromycin was present in ELF. The correlation of these kinetic observations with clinical efficacy or toxicity was not investigated and is unclear, but the data provide a basis for further kinetic and clinical studies.

scholarly journals Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers.

1997 ◽  
Vol 41 (6) ◽  
pp. 1399-1402 ◽  
Author(s):  
K A Rodvold ◽  
M H Gotfried ◽  
L H Danziger ◽  
R J Servi
Keyword(s):  
Steady State ◽  
Standard Deviation ◽  
Bronchoalveolar Lavage ◽  
Drug Administration ◽  
Alveolar Macrophages ◽  
Healthy Adult ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
Adult Volunteers

The steady-state concentrations of clarithromycin and azithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained in intrapulmonary samples during bronchoscopy and bronchoalveolar lavage from 40 healthy, nonsmoking adult volunteers. Mean plasma clarithromycin, 14-(R)-hydroxyclarithromycin, and azithromycin concentrations were similar to those previously reported. Clarithromycin was extensively concentrated in ELF (range of mean +/- standard deviation concentrations, 34.4 +/- 29.3 microg/ml at 4 h to 4.6 +/- 3.7 microg/ml at 24 h) and AM (480 +/- 533 microg/ml at 4 h to 99 +/- 50 microg/ml at 24 h). The concentrations of azithromycin in ELF were 1.01 +/- 0.45 microg/ml at 4 h to 1.22 +/- 0.59 microg/ml at 24 h, and those in AM were 42.7 +/- 28.7 microg/ml at 4 h to 41.7 +/- 12.1 microg/ml at 24 h. The concentrations of 14-(R)-hydroxyclarithromycin in the AM ranged from 89.3 +/- 52.8 microg/ml at 4 h to 31.3 +/- 17.7 microg/ml at 24 h. During the period of 24 h after drug administration, azithromycin and clarithromycin achieved mean concentrations in ELF and AM higher than the concomitant concentrations in plasma.

Solute concentrations of the pulmonary epithelial lining fluid of anesthetized rats

1990 ◽  
Vol 68 (1) ◽  
pp. 275-281 ◽  
Author(s):  
R. M. Effros ◽  
N. H. Feng ◽  
G. Mason ◽  
K. Sietsema ◽  
P. Silverman ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Bronchoalveolar Lavage ◽  
Rat Model ◽  
Total Protein ◽  
Specific Activity ◽  
Epithelial Lining ◽  
Plasma Urea ◽  
Epithelial Lining Fluid ◽  
Plasma Urea Concentration ◽  
Concentration Ratios

Uncertainty persists concerning the best method of estimating the volume and solute concentrations of the pulmonary epithelial lining fluid (ELF) recovered during bronchoalveolar lavage (BAL). In the present study, measurements were made of the BAL-to-plasma concentration ratios of a variety of solutes in an anesthetized rat model. One minute after an intravenous injection of labeled Na+ and urea, 5 ml of isotonic mannitol, saline, or glucose were injected into the trachea and an initial aliquot of the BAL was immediately removed. Initial BAL-to-plasma concentration ratios of urea, Na+, Cl-, Ca2+, and total protein were similar (ranging from 0.013 to 0.017) after BAL with mannitol, but albumin and transferrin ratios were approximately 60% lower and K+ ratios were five times greater. Lavage with saline yielded BAL-to-plasma urea concentration ratios similar to those obtained with mannitol lavage. The BAL-to-plasma specific activity of urea was about twice that of Na+, indicating that urea diffused into the ELF more rapidly than Na+ during the 70 s that elapsed between the time the radioactive urea and Na+ were injected into the circulation and the time when lavage was complete. Subsequent lavage samples also indicated that urea rapidly diffuses into the fluid-filled lungs. These experiments suggest that isotonic mannitol may be a useful solution for lavage, because it allows use of Na+ and perhaps Cl- as additional indicators of ELF dilution by BAL.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Penetration of GSK1322322 into Epithelial Lining Fluid and Alveolar Macrophages as Determined by Bronchoalveolar Lavage

2013 ◽  
Vol 58 (1) ◽  
pp. 419-423 ◽  
Author(s):  
Odin J. Naderer ◽  
Keith A. Rodvold ◽  
Lori S. Jones ◽  
John Z. Zhu ◽  
Chester L. Bowen ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Alveolar Macrophages ◽  
Bacterial Infections ◽  
Time Course ◽  
Respiratory Pathogens ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Concentration Time

ABSTRACTGSK1322322 is a potent peptide deformylase inhibitor within vitroandin vivoactivity against multidrug-resistant skin and respiratory pathogens. This report provides plasma and intrapulmonary pharmacokinetics, safety, and tolerability of GSK1322322 after repeat (twice daily intravenous dosing for 4 days) dosing at 1,500 mg. Plasma samples were collected over the last 12-hour dosing interval of repeat dosing following the day 4 morning dose (the last dose). Bronchoalveolar lavage samples were collected once in each subject, either before or at 2 or 6 h after the last intravenous dose. Plasma area under the concentration-time curve (AUC0–τ) was 66.7 μg · h/ml, and maximum concentration of drug in serum (Cmax) was 25.4 μg/ml following repeat doses of intravenous GSK1322322. The time course of epithelial lining fluid (ELF) and alveolar macrophages (AM) mirrored the plasma concentration-time profile. The AUC0–τfor ELF and AM were 78.9 μg · h/ml and 169 μg · h/ml, respectively. The AUC0–τratios of ELF and AM to total plasma were 1.2 and 2.5, respectively. These ratios increased to 3.5 and 7.4, respectively, when unbound plasma was considered. These results are supportive of GSK1322322 as a potential antimicrobial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. (This study has been registered atClinicalTrials.govunder registration number NCT01610388.)

Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution

1986 ◽  
Vol 60 (2) ◽  
pp. 532-538 ◽  
Author(s):  
S. I. Rennard ◽  
G. Basset ◽  
D. Lecossier ◽  
K. M. O'Donnell ◽  
P. Pinkston ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Bronchoalveolar Lavage ◽  
Lower Respiratory Tract ◽  
Time Course ◽  
Apparent Volume ◽  
The Body ◽  
Albumin Concentration ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
A Value

Bronchoalveolar lavage is a powerful technique for sampling the epithelial lining fluid (ELF) of the lower respiratory tract but also results in a significant dilution of that fluid. To quantify the apparent volume of ELF obtained by bronchoalveolar lavage, urea was used as an endogenous marker of ELF dilution. Since urea diffuses readily through the body, plasma and in situ ELF urea concentrations are identical; thus ELF volume can be calculated using simple dilution principles. Using this approach, we determined that with a standard lavage procedure, the volume of ELF recovered from a normal human is 1.0 +/- 0.1 ml/100 ml of recovered lavage fluid. Time course experiments in which the saline used for lavage was permitted to remain in the lower respiratory tract for various “dwell times” suggested that diffusion of urea from sources other than recovered ELF can contribute to the total urea recovered resulting in an overestimate of the volume of ELF recovered. Thus, while reasonably accurate, the volume of ELF determined by urea must be considered an overestimate, or “apparent” volume. The ELF albumin concentration based on the apparent ELF volume was 3.7 +/- 0.3 mg/ml, a value that is in good agreement with direct measurements made by other techniques in experimental animals. The density of all inflammatory and immune effector cells on the epithelial surface of the lower respiratory tract, based on the apparent ELF volume, was 21,000 +/- 3,000 cells/microliter, a value that is twofold greater than that in blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Reliability of mini-bronchoalveolar lavage for the measurement of epithelial lining fluid concentrations of tobramycin in critically ill patients

2007 ◽  
Vol 33 (9) ◽  
pp. 1519-1523 ◽  
Author(s):  
Emmanuel Boselli ◽  
Dominique Breilh ◽  
Sarah Djabarouti ◽  
Christian Guillaume ◽  
Thomas Rimmelé ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid

Solute exchange between the plasma and epithelial lining fluid of rat lungs

1992 ◽  
Vol 72 (3) ◽  
pp. 1081-1089 ◽  
Author(s):  
N. H. Feng ◽  
A. Hacker ◽  
R. M. Effros
Keyword(s):  
Plasma Concentration ◽  
Bronchoalveolar Lavage ◽  
Molecular Mass ◽  
Evans Blue ◽  
Serum Proteins ◽  
Human Albumin ◽  
Epithelial Lining ◽  
Blood Concentrations ◽  
Epithelial Lining Fluid ◽  
Solute Exchange

Although the transport of solutes from air spaces to plasma has been extensively studied, comparatively little information is available concerning solute equilibration between the plasma and the epithelial lining fluid (ELF) of air-filled lungs. In the present study, 11 lipophobic indicators varying in molecular mass between 22 and 80,000 Da were injected intravenously and/or intramuscularly into anesthetized rats in a manner designed to keep blood concentrations constant. The animals were killed by rapid lavage of their lungs at various intervals up to 120 min after the injections had been made. Indicator concentrations in the bronchoalveolar lavage (BAL) fluid and plasma were determined, and BAL-to-plasma concentration ratios were calculated for indicators that were injected (exogenous: [14C]urea, 22Na+, [3H]mannitol, 99mTc-diethylenetriaminepentaacetate (a chelate), 51Cr-(ethylene dinitrilo)tetraacetate (a chelate), 113mIn-transferrin, human albumin, and Evans blue-labeled rat albumin) and those that were already present from the plasma and ELF (unlabeled urea, rat albumin, and rat transferrin). Leakage of exogenous indicators in the blood into the BAL fluid was observed during the lavage procedure. Leakage of [14C]urea, 22Na+, and [3H]mannitol exceeded that of the heavier solute molecules. Diffusion of proteins and the labeled chelates into the ELF before lavage occurred at similar rates, suggesting vesicular transport. Use of rapidly diffusible solutes such as urea for determining dilution of ELF by BAL should be accompanied by intravascular injections of labeled solutes to correct for diffusion from the blood during lavage. Alternatively, labeled chelates or serum proteins can be used to estimate dilution of ELF by BAL. Interstitial sampling may be inevitable if the epithelium has been injured before lavage.

scholarly journals Microdosing as a Potential Tool to Enhance Clinical Development of Novel Antibiotics: A Tissue and Plasma PK Feasibility Study with Ciprofloxacin

2022 ◽  
Author(s):  
Zoe Oesterreicher ◽  
Sabine Eberl ◽  
Beatrix Wulkersdorfer ◽  
Peter Matzneller ◽  
Claudia Eder ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Bronchoalveolar Lavage ◽  
Therapeutic Dose ◽  
Subcutaneous Tissue ◽  
Epithelial Lining ◽  
Clinical Trial Registration ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Concentration Time ◽  
Drug Concentrations

Abstract Background and Objective In microdose studies, drug pharmacokinetics is measured in humans after administration of subtherapeutic doses. While previous microdose studies focused primarily on plasma pharmacokinetics, we set out to evaluate the feasibility of microdosing for a pharmacokinetic assessment in subcutaneous tissue and epithelial lining fluid. Methods Healthy subjects received a single intravenous bolus injection of a microdose of [14C]ciprofloxacin (1.1 µg, 7 kBq) with (cohort A, n = 9) or without (cohort B, n = 9) a prior intravenous infusion of a therapeutic dose of unlabeled ciprofloxacin (400 mg). Microdialysis and bronchoalveolar lavage were applied for determination of subcutaneous and intrapulmonary drug concentrations. Microdose [14C]ciprofloxacin was quantified by accelerator mass spectrometry and therapeutic-dose ciprofloxacin by liquid chromatography–tandem mass spectrometry. Results The pharmacokinetics of therapeutic-dose ciprofloxacin (cohort A) in plasma, subcutaneous tissue, and epithelial lining fluid was in accordance with previous data. In plasma and subcutaneous tissue, the dose-adjusted area under the concentration–time curve of microdose ciprofloxacin was similar in cohorts A and B and within an 0.8-fold to 1.1-fold range of the area under the concentration–time curve of therapeutic-dose ciprofloxacin. Penetration of microdose ciprofloxacin into subcutaneous tissue was similar in cohorts A and B and comparable to that of therapeutic-dose ciprofloxacin with subcutaneous tissue-to-plasma area under the concentration–time curve ratios of 0.44, 0.44, and 0.38, respectively. Penetration of microdose ciprofloxacin into epithelial lining fluid was highly variable and failed to predict the epithelial lining fluid penetration of therapeutic-dose ciprofloxacin. Conclusions Our study confirms the feasibility of microdosing for pharmacokinetic measurements in plasma and subcutaneous tissue. Microdosing combined with microdialysis is a potentially useful tool in clinical antimicrobial drug development, but its applicability for the assessment of pulmonary pharmacokinetics with bronchoalveolar lavage requires further studies. Clinical Trial Registration ClinicalTrials.gov NCT03177720 (registered 6 June, 2017).

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