Evaluation of the concentration of marbofloxacin in alveolar macrophages and pulmonary epithelial lining fluid after administration in dogs

2005 ◽  
Vol 66 (10) ◽  
pp. 1770-1774 ◽  
Author(s):  
Harry W. Boothe ◽  
Sarah A. Jones ◽  
W. Scott Wilkie ◽  
Albert Boeckh ◽  
Kristol K. Stenstrom ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid

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.

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.)

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