JAC Advance Access published online on July 29, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg355
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Pulmonary Associates and School of Medicine, University
of Arizona, Phoenix, AZ; College of Pharmacy, University of Illinois,
833 South Wood Street, Chicago, IL 60612, USA
* Corresponding author. E-mail: kar{at}uic.edu.
Received 6 January 2003
; revised 19 May 2003
; accepted 2 June 2003
Objectives: The steady-state concentrations
of clarithromycin in plasma were compared with concomitant concentrations
in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained
from intrapulmonary samples during bronchoscopy and bronchoalveolar
lavage (BAL). Concentrations of the major metabolite, 14-hydroxyclarithromycin,
were also determined in plasma and AM. Materials and methods: Forty-two healthy, non-smoking
adult subjects (age: 18-54 years; 19 females, 23 males)
received oral clarithromycin extended-release formulation (1000
mg once daily for five consecutive days). Bronchoscopy and BAL were
carried out once in each subject at either 3, 6, 9, 12, 24 or 48
h after the last administered dose of clarithromycin. In addition,
three subjects who did not take clarithromycin served as controls
and underwent bronchoscopy at 0 h. Drug concentrations in plasma,
ELF, and AM were determined by high-performance liquid chromatography. Results: Clarithromycin was extensively concentrated
in ELF [range of mean (±S.D.)
concentrations: 6.38 ± 3.92
to 11.50 ± 6.65 mg/L] and AM
(127.0 ± 61.5 to 573.8 ± 309.3
mg/L) than simultaneous plasma concentration (0.75 ± 0.31
to 2.22 ± 0.72 mg/L). The ranges of
mean (±S.D.) concentrations
of 14-hydroxyclarithromycin in plasma and AM were 0.52 ± 0.29
to 0.80 ± 0.31 mg/L and 22.1 ± 13.5
to 49.5 ± 16.2 mg/L, respectively. Conclusions: Once-daily dosing of extended-release
formulation clarithromycin 1000 mg produced significantly (P < 0.05)
higher steady-state concentrations of clarithromycin in ELF (2-14
times) and AM (50-700 times) compared to
simultaneous plasma concentrations throughout the 24 h period after
drug administration. The 14-hydroxy metabolite of clarithromycin
achieved significantly (P < 0.05) higher
steady-state concentrations in AM (18-180 times)
compared with concurrent plasma concentrations.
Keywords: pharmacokinetics, bronchoscopy, epithelial lining
fluid, alveolar macrophages
Steady-state plasma and bronchopulmonary characteristics
of clarithromycin extended-release tablets in normal healthy
adult subjects
2 Colleges of Pharmacy and Medicine, University of Illinois,
833 South Wood Street, Chicago, IL 60612, USA
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