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Antimicrobial Agents and Chemotherapy, August 2003, p. 2450-2457, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2450-2457.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Steady-State Plasma and Bronchopulmonary Concentrations of Intravenous Levofloxacin and Azithromycin in Healthy Adults

Keith A. Rodvold,1,2* Larry H. Danziger,1,2 and Mark H. Gotfried1,3,4

Colleges of Pharmacy,1 Medicine, University of Illinois, Chicago, Illinois,2 School of Medicine, University of Arizona,3 Pulmonary Associates, Phoenix, Arizona4

Received 25 November 2002/ Returned for modification 28 February 2003/ Accepted 5 May 2003

The purpose of this study was to compare the concentrations of levofloxacin and azithromycin in steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) after intravenous administration. Thirty-six healthy, nonsmoking adult subjects were randomized to either intravenous levofloxacin (500 or 750 mg) or azithromycin (500 mg) once daily for five doses. Venipuncture and bronchoscopy with bronchoalveolar lavage were performed in each subject at either 4, 12, or 24 h after the start of the last antibiotic infusion. The mean concentrations of levofloxacin and azithromycin in plasma were similar to those previously published. The dosing regimens of levofloxacin achieved significantly (P < 0.05) higher concentrations in steady-state plasma than azithromycin during the 24 h after drug administration. The respective mean (± standard deviation) concentrations at 4, 12, and 24 h in ELF for 500 mg of levofloxacin were 11.01 ± 4.52, 2.50 ± 0.97, and 1.24 ± 0.55 µg/ml; those for 750 mg of levofloxacin were 12.94 ± 1.21, 6.04 ± 0.39, and 1.73 ± 0.78 µg/ml; and those for azithromycin were 1.70 ± 0.74, 1.27 ± 0.47, and 2.86 ± 1.75 µg/ml. The differences in concentrations in ELF among the two levofloxacin groups and azithromycin were significantly (P < 0.05) higher at the 4- and 12-h sampling times. The respective concentrations in AM for 500 mg of levofloxacin were 83.9 ± 53.2, 18.3 ± 6.7, and 5.6 ± 3.2 µg/ml; those for 750 mg of levofloxacin were 81.7 ± 37.0, 78.2 ± 55.4, and 13.3 ± 6.5 µg/ml; and those for azithromycin were 650 ± 259, 669 ± 311, and 734 ± 770 µg/ml. Azithromycin achieved significantly (P < 0.05) higher concentrations in AM than levofloxacin at all sampling times. The concentrations in ELF and AM following intravenous administration of levofloxacin and azithromycin were higher than concentrations in plasma. Further studies are needed to determine the clinical significance of such high intrapulmonary concentrations in patients with respiratory tract infections.

* Corresponding author. Mailing address: m/c 886, Pharmacy Practice, University of Illinois at Chicago, College of Pharmacy, Room 164, 833 South Wood St., Chicago, Illinois 60612. Phone: (312) 996-3341. Fax: (312) 413-1797. E-mail: kar{at}uic.edu.

Antimicrobial Agents and Chemotherapy, August 2003, p. 2450-2457, Vol. 47, No. 8
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.8.2450-2457.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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