Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men

ABSTRACT Ethionamide, 250 mg every 12 h for a total of nine doses, was administered to 40 adult volunteers (10 men with AIDS, 10 healthy men, 10 women with AIDS, and 10 healthy women). Blood was obtained for drug assay prior to administration of the first dose, 2 h after the last dose, and at the completion of standardized bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Ethionamide was measured in epithelial lining fluid (ELF) and alveolar cells (AC) using a new mass spectrometric method. The presence of AIDS or gender was without significant effect on the concentrations of ethionamide in plasma, AC, or ELF. Plasma concentrations (mean ± standard deviation [SD]) were 0.97 ± 0.65 and 0.65 ± 0.35 μg/ml at 2 and 4 h after the last dose, respectively, and both values were significantly greater than the concentration of ethionamide in AC (0.38 ± 0.47 μg/ml) (P < 0.05). The concentration of ethionamide was significantly greater in ELF (5.63 ± 3.8 μg/ml) than in AC or plasma at 2 and 4 h and was approximately 10 to 20 times the reported MIC for ethionamide-susceptible strains of Mycobacterium tuberculosis. For all 40 subjects, the ELF/plasma concentration ratios (mean ± SD) at 2 and 4 h were 8.7 ± 11.7 and 9.7 ± 5.6, respectively. We conclude that the absorption of orally administered ethionamide, as measured in this study, was not affected by gender or the presence of AIDS. Ethionamide concentrations were significantly greater in ELF than in plasma or AC, suggesting that substantial antimycobacterial activity resides in this compartment.

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

American Journal of Veterinary Research ◽

10.2460/ajvr.2005.66.1770 ◽

2005 ◽

Vol 66 (10) ◽

pp. 1770-1774 ◽

Cited By ~ 8

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

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Aerosol-based efficient delivery of telithromycin, a ketolide antimicrobial agent, to lung epithelial lining fluid and alveolar macrophages for treatment of respiratory infections

Drug Development and Industrial Pharmacy ◽

10.3109/03639040903551319 ◽

2010 ◽

Vol 36 (7) ◽

pp. 861-866 ◽

Cited By ~ 12

Author(s):

Kohei Togami ◽

Sumio Chono ◽

Toshinobu Seki ◽

Kazuhiro Morimoto

Keyword(s):

Antimicrobial Agent ◽

Alveolar Macrophages ◽

Respiratory Infections ◽

Epithelial Lining ◽

Epithelial Lining Fluid ◽

Efficient Delivery ◽

Lung Epithelial

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.6.1399 ◽

1997 ◽

Vol 41 (6) ◽

pp. 1399-1402 ◽

Cited By ~ 139

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.

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