title: Pharmacokinetics of arbekacin in bronchial epithelial lining fluid of healthy volunteers.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Yohei
authors: Y
authors: Funatsu
authors: Center for Infectious Diseases and Infection Control, Keio University, School of Medicine, Tokyo, Japan. Electronic address: n-hasegawa@z8.keio.jp.
authors: Naoki
authors: N
authors: Hasegawa
authors: Center for Infectious Diseases and Infection Control, Keio University, School of Medicine, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Fujiwara
authors: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Ho
authors: H
authors: Namkoong
authors: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Takahiro
authors: T
authors: Asami
authors: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Sadatomo
authors: S
authors: Tasaka
authors: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Yoshifumi
authors: Y
authors: Kimizuka
authors: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Hirofumi
authors: H
authors: Kamata
authors: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Makoto
authors: M
authors: Ishii
authors: Center for Infectious Diseases and Infection Control, Keio University, School of Medicine, Tokyo, Japan.
authors: Osamu
authors: O
authors: Iketani
authors: Center for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, Tokyo, Japan.
authors: Haruhiko
authors: H
authors: Ogata
authors: Center for Infectious Diseases and Infection Control, Keio University, School of Medicine, Tokyo, Japan.
authors: Satoshi
authors: S
authors: Iwata
authors: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors: Tomoko
authors: T
authors: Betsuyaku
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D001980:Bronchi / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004848:Epithelium / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D020545:Respiratory Mucosa / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D003982:Dibekacin; C031986:arbekacin
keywords: Aminoglycoside; Arbekacin; Bronchoscopic microsampling; Epithelial lining fluid; Methicillin-resistant Staphylococcus aureus; Pharmacokinetic/pharmacodynamic