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J Infect Chemother. 2014 Oct;20(10):607-11. doi: 10.1016/j.jiac.2014.05.007. Epub 2014 Jun 25.

Pharmacokinetics of arbekacin in bronchial epithelial lining fluid of healthy volunteers.

Author information

1
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
2
Center for Infectious Diseases and Infection Control, Keio University, School of Medicine, Tokyo, Japan. Electronic address: n-hasegawa@z8.keio.jp.
3
Center for Infectious Diseases and Infection Control, Keio University, School of Medicine, Tokyo, Japan.
4
Center for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, Tokyo, Japan.

Abstract

INTRODUCTION:

Arbekacin is a unique aminoglycoside antibiotic with anti-methicillin-resistant Staphylococcus aureus activity. The efficacy of aminoglycosides is related to their serum maximum concentration. Local concentration of antibiotics in pulmonary epithelial lining fluid, rather than its serum concentration, can help determine its clinical efficacy more precisely for treatment of respiratory infectious disease. The objective of this study was to sequentially measure arbekacin concentration in epithelial lining fluid after infusion of a single clinically available dose.

METHOD:

After the initial blood sampling, arbekacin was intravenously infused into 6 healthy volunteers over 1 h. Epithelial lining fluid and serum samples were collected by bronchoscopic microsampling 1, 1.5, 2, 2.5, 3, 4, 5, and 6 h after the start of 200 mg arbekacin infusion.

RESULTS:

Each probe sampled 10.1 ± 5.2 μl bronchial epithelial lining fluid. The sample dilution factor was 266.7 ± 157.1. Drug concentration was successfully measured in all but 2 of the epithelial lining fluid samples. The maximum concentration of arbekacin in epithelial lining fluid and serum was 10.4 ± 1.9 μg/ml and 26.0 ± 12.2 μg/ml, respectively. The ratio of the maximum drug concentration in the epithelial lining fluid to that in the serum was 0.47 ± 0.19.

CONCLUSIONS:

The maximum concentration of epithelial lining fluid reached levels that would effectively treat most clinical strains of methicillin-resistant S. aureus.

KEYWORDS:

Aminoglycoside; Arbekacin; Bronchoscopic microsampling; Epithelial lining fluid; Methicillin-resistant Staphylococcus aureus; Pharmacokinetic/pharmacodynamic

PMID:
24973909
DOI:
10.1016/j.jiac.2014.05.007
[Indexed for MEDLINE]
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