Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid

Background and 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.