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Antimicrobial Agents and Chemotherapy, Oct 1996, 2375-2379, Vol 40, No. 10
Copyright © 1996 by the American Society for Microbiology. All rights reserved.

Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin

KB Patel, D Xuan, PR Tessier, JH Russomanno, R Quintiliani and CH Nightingale
Department of Pharmacy Practice, Arnold and Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, New York 11201, USA.

The bronchopulmonary and plasma pharmacokinetics of clarithromycin (CLA; 500 mg given twice daily for nine doses) or azithromycin (AZ; 500 mg for the first dose and then 250 mg once daily for four doses) were assessed in 41 healthy nonsmokers. Bronchoalveolar lavage was performed at 4, 8, 12, or 24 h after administration of the last dose. The concentrations (mean +/- standard deviation) of CLA, 14- hydroxyclarithromycin, and AZ were measured in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) cells by high- performance liquid chromatography assay. The concentrations of CLA achieved in ELF were 34.02 +/- 5.16 micrograms/ml at 4 h, 20.63 +/- 4.49 micrograms/ml at 8 h, 23.01 +/- 11.9 micrograms/ml at 12 h, and 4.17 +/- 0.29 microgram/ml at 24 h, whereas at the same time points AZ concentrations remained below the limit of assay sensitivity (0.01 microgram/ml) for all but two subjects. The concentrations of CLA in the AM cells were significantly higher than those of AZ at 8 h (703 +/- 235 and 388 +/- 53 micrograms/ml, respectively). However, the ratio of the concentration in AM cells/concentration in plasma was significantly higher for AZ than for CLA for all time points because of the lower concentration of AZ in plasma. These results indicate that while AZ has higher tissue concentration to plasma ratios, as shown by other investigators, the absolute concentrations of CLA in AM cells and ELF are higher for up to 8 and 12 h, respectively, after administration of the last dose.


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