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 Bronchopulmonary Disposition of Micafungin in Healthy Adult Volunteers

2008 ◽  
Vol 53 (3) ◽  
pp. 1218-1220 ◽  
Author(s):  
Anthony M. Nicasio ◽  
Pamela R. Tessier ◽  
David P. Nicolau ◽  
R. Fredrick Knauft ◽  
John Russomanno ◽  
...  
Keyword(s):  
Steady State ◽  
Bronchoalveolar Lavage ◽  
Healthy Volunteers ◽  
Alveolar Macrophages ◽  
Healthy Adult ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
The Third ◽  
Adult Volunteers

ABSTRACT By way of bronchoscopy and bronchoalveolar lavage, intrapulmonary steady-state concentrations of micafungin administered at 150 mg daily to 15 healthy volunteers were determined at 4, 12, and 24 h after the third dose. The micafungin disposition was predominantly intracellular, with approximately 106% penetration into alveolar macrophages and 5% penetration into epithelial lining fluid.

scholarly journals Intrapulmonary Pharmacokinetics of Lascufloxacin in Healthy Adult Volunteers

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Hidetoshi Furuie ◽  
Sayoko Tanioka ◽  
Keiko Shimizu ◽  
Shigeru Manita ◽  
Masaharu Nishimura ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Healthy Adult ◽  
Respiratory Pathogens ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Drug Concentrations ◽  
Healthy Adult Male ◽  
Registration Number ◽  
Adult Volunteers

ABSTRACT This study was performed to investigate the intrapulmonary penetration of lascufloxacin in humans. Thirty healthy adult male Japanese subjects, allocated into five groups, received lascufloxacin in a single oral dose of 75 mg. Bronchoalveolar lavage and blood sampling were performed simultaneously in each subject at 1, 2, 4, 6, or 24 h after administration, and lascufloxacin concentrations in plasma, epithelial lining fluid, and alveolar macrophages were determined. Lascufloxacin was rapidly distributed to the epithelial lining fluid with a time to maximum drug concentration ( T max ) of 1 h, which was identical to that in plasma. The maximum concentration of drug ( C max ) values in plasma, epithelial lining fluid, and alveolar macrophages were 0.576, 12.3, and 21.8 μg/ml, respectively. The corresponding area under the concentration-time curve from 0 to 24 h (AUC 0–24 ) values were 7.67, 123, and 325 μg · h/ml. The mean drug concentrations in the epithelial lining fluid and alveolar macrophages were much higher than those in plasma at all time points examined, and the average site-to-free plasma concentration ratios fell within the ranges of 57.5 to 86.4 and 71.0 to 217, respectively. Drug levels in epithelial lining fluid and alveolar macrophages exceeded the MIC 90 values for common respiratory pathogens. (This study was registered at JAPIC under registration number JapicCTI-142547.)

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

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.)

Steady-State Pharmacokinetics of Darunavir/Ritonavir and Pitavastatin when Co-administered to Healthy Adult Volunteers

2014 ◽  
Vol 34 (7) ◽  
pp. 475-482 ◽  
Author(s):  
Christine Y. Yu ◽  
Stuart E. Campbell ◽  
Craig A. Sponseller ◽  
David S. Small ◽  
Matthew M. Medlock ◽  
...  
Keyword(s):  
Steady State ◽  
Healthy Adult ◽  
Adult Volunteers

scholarly journals Effects of AIDS and Gender on Steady-State Plasma and Intrapulmonary Ethionamide Concentrations

2000 ◽  
Vol 44 (5) ◽  
pp. 1337-1341 ◽  
Author(s):  
John E. Conte ◽  
Jeffrey A. Golden ◽  
Mari McQuitty ◽  
Juliana Kipps ◽  
Emil T. Lin ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Antimycobacterial Activity ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Epithelial Lining ◽  
Alveolar Cells ◽  
Epithelial Lining Fluid ◽  
Healthy Men ◽  
And Gender ◽  
Adult Volunteers

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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