Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid

Eiki Kikuchi, Koichi Yamazaki, Junko Kikuchi, Naoki Hasegawa, Satoru Hashimoto, Akitoshi Ishizaka, Masaharu Nishimura

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 (Cmax) of clarithromycin was 0.36 ± 0.07 mg/L in serum and 1.44 ± 0.49 mg/L in bronchial ELF (P < 0.01). Cmax 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 (AUC0-10) 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 AUC0-10 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.

Original languageEnglish
Pages (from-to)221-226
Number of pages6
JournalRespirology
Volume13
Issue number2
DOIs
Publication statusPublished - 2008 Mar

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Clarithromycin
Pharmacokinetics
Alveolar Macrophages
Dimercaprol
Serum
Oral Administration
Healthy Volunteers
Anti-Bacterial Agents

Keywords

  • Anti-infective agent
  • BAL
  • Bronchoscopy
  • Clarithromycin
  • Extracellular fluid
  • pharmacokinetics

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Kikuchi, E., Yamazaki, K., Kikuchi, J., Hasegawa, N., Hashimoto, S., Ishizaka, A., & Nishimura, M. (2008). Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid. Respirology, 13(2), 221-226. https://doi.org/10.1111/j.1440-1843.2007.01208.x

Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid. / Kikuchi, Eiki; Yamazaki, Koichi; Kikuchi, Junko; Hasegawa, Naoki; Hashimoto, Satoru; Ishizaka, Akitoshi; Nishimura, Masaharu.

In: Respirology, Vol. 13, No. 2, 03.2008, p. 221-226.

Research output: Contribution to journalArticle

Kikuchi, E, Yamazaki, K, Kikuchi, J, Hasegawa, N, Hashimoto, S, Ishizaka, A & Nishimura, M 2008, 'Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid', Respirology, vol. 13, no. 2, pp. 221-226. https://doi.org/10.1111/j.1440-1843.2007.01208.x
Kikuchi, Eiki ; Yamazaki, Koichi ; Kikuchi, Junko ; Hasegawa, Naoki ; Hashimoto, Satoru ; Ishizaka, Akitoshi ; Nishimura, Masaharu. / Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid. In: Respirology. 2008 ; Vol. 13, No. 2. pp. 221-226.
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abstract = "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 (Cmax) of clarithromycin was 0.36 ± 0.07 mg/L in serum and 1.44 ± 0.49 mg/L in bronchial ELF (P < 0.01). Cmax 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 (AUC0-10) 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 AUC0-10 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.",
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T1 - Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid

AU - Kikuchi, Eiki

AU - Yamazaki, Koichi

AU - Kikuchi, Junko

AU - Hasegawa, Naoki

AU - Hashimoto, Satoru

AU - Ishizaka, Akitoshi

AU - Nishimura, Masaharu

PY - 2008/3

Y1 - 2008/3

N2 - 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 (Cmax) of clarithromycin was 0.36 ± 0.07 mg/L in serum and 1.44 ± 0.49 mg/L in bronchial ELF (P < 0.01). Cmax 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 (AUC0-10) 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 AUC0-10 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.

AB - 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 (Cmax) of clarithromycin was 0.36 ± 0.07 mg/L in serum and 1.44 ± 0.49 mg/L in bronchial ELF (P < 0.01). Cmax 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 (AUC0-10) 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 AUC0-10 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.

KW - Anti-infective agent

KW - BAL

KW - Bronchoscopy

KW - Clarithromycin

KW - Extracellular fluid

KW - pharmacokinetics

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