Concentrations of clarithromycin and active metabolite in the epithelial lining fluid of patients with Mycobacterium avium complex pulmonary disease

Naoki Hasegawa, Tomoyasu Nishimura, Masazumi Watabnabe, Sadatomo Tasaka, Yasushi Nakano, Koichi Yamazaki, Satoru Hashimoto, Masahiro Nishimura, Akitoshi Ishizaka

Research output: Contribution to journalArticle

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Abstract

Objectives: Clarithromycin (CAM) is widely accepted for the treatment of Mycobacterium avium complex (MAC) pulmonary diseases. This study measured (a) the concentrations of CAM and its active metabolite (14OH-CAM) in bronchial epithelial lining fluid (ELF) obtained by bronchoscopic microsampling (BMS), and (b) the minimal inhibitory concentrations (MIC) of CAM for each MAC isolate. Methods: We studied eight patients with MAC pulmonary disease treated with oral CAM, 400 (n = 4) or 800 (n = 4) mg/day. BMS was performed 3 h after the last CAM dose, and the concentrations of CAM and 14OH-CAM were measured in ELF collected from the diseased and normal contralateral pulmonary segments, and in serum. Results: The mean ± SEM ELF concentrations of CAM (23.85 ± 7.64 μg/ml) and CAM + 14OH-CAM (28.71 ± 8.37 μg/ml) in the 800 mg/day treatment group were significantly higher than in the 400 mg/day group (7.48 ± 2.58 μg/ml and 9.63 ± 2.99 μg/ml, respectively; both p < 0.05), while the serum concentrations were similar in both groups. In both treatment groups, the mean ELF concentrations sampled from diseased and normal segments were higher than the MIC against MAC isolates. The mean ELF concentration of CAM in the 400 mg/day treatment group was <8 μg/ml (the breakpoint concentration of CAM against M. avium recommended by the Clinical Laboratories Standards Institute), while the mean concentration in the 800 mg/day treatment group was >8 μg/ml. Conclusion: These observations suggest that CAM, 800 mg/day, is an appropriate dose to treat MAC pulmonary disease, and prevent its spread from diseased to non-diseased lung segments.

Original languageEnglish
Pages (from-to)190-193
Number of pages4
JournalPulmonary Pharmacology and Therapeutics
Volume22
Issue number3
DOIs
Publication statusPublished - 2009 Jun

Fingerprint

Mycobacterium avium Complex
Pulmonary diseases
Clarithromycin
Metabolites
Linings
Lung Diseases
Fluids
Lung

Keywords

  • Antimicrobial concentration
  • Bronchoscopic microsampling
  • Clarithromycin
  • Epithelial lining fluid
  • Mycobacterium avium complex

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology (medical)
  • Biochemistry, medical

Cite this

Concentrations of clarithromycin and active metabolite in the epithelial lining fluid of patients with Mycobacterium avium complex pulmonary disease. / Hasegawa, Naoki; Nishimura, Tomoyasu; Watabnabe, Masazumi; Tasaka, Sadatomo; Nakano, Yasushi; Yamazaki, Koichi; Hashimoto, Satoru; Nishimura, Masahiro; Ishizaka, Akitoshi.

In: Pulmonary Pharmacology and Therapeutics, Vol. 22, No. 3, 06.2009, p. 190-193.

Research output: Contribution to journalArticle

Hasegawa, Naoki ; Nishimura, Tomoyasu ; Watabnabe, Masazumi ; Tasaka, Sadatomo ; Nakano, Yasushi ; Yamazaki, Koichi ; Hashimoto, Satoru ; Nishimura, Masahiro ; Ishizaka, Akitoshi. / Concentrations of clarithromycin and active metabolite in the epithelial lining fluid of patients with Mycobacterium avium complex pulmonary disease. In: Pulmonary Pharmacology and Therapeutics. 2009 ; Vol. 22, No. 3. pp. 190-193.
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abstract = "Objectives: Clarithromycin (CAM) is widely accepted for the treatment of Mycobacterium avium complex (MAC) pulmonary diseases. This study measured (a) the concentrations of CAM and its active metabolite (14OH-CAM) in bronchial epithelial lining fluid (ELF) obtained by bronchoscopic microsampling (BMS), and (b) the minimal inhibitory concentrations (MIC) of CAM for each MAC isolate. Methods: We studied eight patients with MAC pulmonary disease treated with oral CAM, 400 (n = 4) or 800 (n = 4) mg/day. BMS was performed 3 h after the last CAM dose, and the concentrations of CAM and 14OH-CAM were measured in ELF collected from the diseased and normal contralateral pulmonary segments, and in serum. Results: The mean ± SEM ELF concentrations of CAM (23.85 ± 7.64 μg/ml) and CAM + 14OH-CAM (28.71 ± 8.37 μg/ml) in the 800 mg/day treatment group were significantly higher than in the 400 mg/day group (7.48 ± 2.58 μg/ml and 9.63 ± 2.99 μg/ml, respectively; both p < 0.05), while the serum concentrations were similar in both groups. In both treatment groups, the mean ELF concentrations sampled from diseased and normal segments were higher than the MIC against MAC isolates. The mean ELF concentration of CAM in the 400 mg/day treatment group was <8 μg/ml (the breakpoint concentration of CAM against M. avium recommended by the Clinical Laboratories Standards Institute), while the mean concentration in the 800 mg/day treatment group was >8 μg/ml. Conclusion: These observations suggest that CAM, 800 mg/day, is an appropriate dose to treat MAC pulmonary disease, and prevent its spread from diseased to non-diseased lung segments.",
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AU - Hasegawa, Naoki

AU - Nishimura, Tomoyasu

AU - Watabnabe, Masazumi

AU - Tasaka, Sadatomo

AU - Nakano, Yasushi

AU - Yamazaki, Koichi

AU - Hashimoto, Satoru

AU - Nishimura, Masahiro

AU - Ishizaka, Akitoshi

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AB - Objectives: Clarithromycin (CAM) is widely accepted for the treatment of Mycobacterium avium complex (MAC) pulmonary diseases. This study measured (a) the concentrations of CAM and its active metabolite (14OH-CAM) in bronchial epithelial lining fluid (ELF) obtained by bronchoscopic microsampling (BMS), and (b) the minimal inhibitory concentrations (MIC) of CAM for each MAC isolate. Methods: We studied eight patients with MAC pulmonary disease treated with oral CAM, 400 (n = 4) or 800 (n = 4) mg/day. BMS was performed 3 h after the last CAM dose, and the concentrations of CAM and 14OH-CAM were measured in ELF collected from the diseased and normal contralateral pulmonary segments, and in serum. Results: The mean ± SEM ELF concentrations of CAM (23.85 ± 7.64 μg/ml) and CAM + 14OH-CAM (28.71 ± 8.37 μg/ml) in the 800 mg/day treatment group were significantly higher than in the 400 mg/day group (7.48 ± 2.58 μg/ml and 9.63 ± 2.99 μg/ml, respectively; both p < 0.05), while the serum concentrations were similar in both groups. In both treatment groups, the mean ELF concentrations sampled from diseased and normal segments were higher than the MIC against MAC isolates. The mean ELF concentration of CAM in the 400 mg/day treatment group was <8 μg/ml (the breakpoint concentration of CAM against M. avium recommended by the Clinical Laboratories Standards Institute), while the mean concentration in the 800 mg/day treatment group was >8 μg/ml. Conclusion: These observations suggest that CAM, 800 mg/day, is an appropriate dose to treat MAC pulmonary disease, and prevent its spread from diseased to non-diseased lung segments.

KW - Antimicrobial concentration

KW - Bronchoscopic microsampling

KW - Clarithromycin

KW - Epithelial lining fluid

KW - Mycobacterium avium complex

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