title: Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid.
abstract: OBJECTIVE
  BAL is an established technique for measuring antibiotic concentrations in the epithelial lining fluid (ELF) of the bronchiolar-alveolar regions. However, the results may not reflect concentrations in bronchial regions. Bronchoscopic microsampling (BMS) is a technique for repeated sampling of bronchial ELF. The objective of the present study was to determine the time versus concentration profile of clarithromycin and its active metabolite, 14-hydroxy-clarithromycin, in bronchial ELF, as determined by BMS.
  
  
  METHODS
  BMS was performed at 1, 2, 3, 5 and 10 h after a single oral administration of 200 mg clarithromycin in five healthy volunteers. BAL was performed 3 h after administration to determine clarithromycin concentrations in alveolar ELF and alveolar macrophages (AM).
  
  
  RESULTS
  The maximum concentration (C(max)) of clarithromycin was 0.36 +/- 0.07 mg/L in serum and 1.44 +/- 0.49 mg/L in bronchial ELF (P < 0.01). C(max) for 14-hydroxy-clarithromycin was 0.34 +/- 0.13 mg/L in serum and 0.68 +/- 0.34 mg/L in bronchial ELF. The area under the concentration-time curve from 0 to 10 h (AUC(0-10)) for clarithromycin was 2.10 +/- 0.49 mg.h/L for serum and 7.37 +/- 2.07 mg.h/L for bronchial ELF (P < 0.01). The concentrations of clarithromycin in alveolar ELF and AM, 3 h after oral administration, were 4.84 +/- 3.39 mg/L and 10.7 +/- 8.7 mg/L, respectively.
  
  
  CONCLUSIONS
  A single oral dose of clarithromycin produces a significantly higher C(max) and AUC(0-10) for clarithromycin in bronchial ELF than in serum, and higher concentrations in alveolar ELF and AM than in serum. BMS might be useful for measuring the pharmacokinetic profile of clarithromycin in bronchial ELF.
authors.affiliation: First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Kikuchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Junko
authors.initials: J
authors.lastname: Kikuchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Hasegawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001980:Bronchi / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D017291:Clarithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D020545:Respiratory Mucosa / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin