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Clinical Investigations: ANTIBIOTICS |

Steady-State Plasma and Intrapulmonary Concentrations of Levofloxacin and Ciprofloxacin in Healthy Adult Subjects*

Mark H. Gotfried, MD, FCCP; Larry H. Danziger, PharmD; Keith A. Rodvold, PharmD
Author and Funding Information

*From the Pulmonary Associates PA (Dr. Gotfried), University of Arizona, Phoenix, AZ; and the College of Pharmacy (Drs. Danziger and Rodvold), University of Illinois, Chicago, IL.

Correspondence to: Keith A. Rodvold, PharmD, m/c 886, Pharmacy Practice, University of Illinois at Chicago, College of Pharmacy, Room 164, 833 South Wood St, Chicago, IL 60612; e-mail: kar@uic.edu



Chest. 2001;119(4):1114-1122. doi:10.1378/chest.119.4.1114
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Published online

Study objective: To determine the steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levofloxacin and ciprofloxacin.

Design: Multiple-dose, open-label, randomized pharmacokinetic study.

Participants: Thirty-six healthy, nonsmoking adult subjects were randomized either to oral levofloxacin, 500 or 750 mg once daily for five doses, or ciprofloxacin, 500 mg q12h for nine doses. Interventions: Venipuncture, bronchoscopy, and BAL were performed in each subject at 4 h, 12 h, or 24 h after the last administered dose of antibiotic.

Measurement and results: Mean plasma concentrations of levofloxacin and ciprofloxacin were similar to those previously reported. For once-daily dosing of levofloxacin, 500 mg, the mean (± SD) steady-state concentrations at 4 h, 12 h, and 24 h in ELF were 9.9 ± 2.7μ g/mL, 6.5 ± 2.5 μg/mL, and 0.7 ± 0.4 μg/mL, respectively; AM concentrations were 97.9 ± 80.0 μg/mL, 36.7 ± 23.4 μg/mL, and 13.8 ± 16.0 μg/mL, respectively. For levofloxacin, 750 mg, the mean steady-state concentrations in ELF were 22.1 ± 14.9 μg/mL, 9.2 ± 5.3 μg/mL, and 1.5 ± 0.8 μg/mL, respectively; AM concentrations were 105.1 ± 65.5 μg/mL, 36.2 ± 26.1 μg/mL, and 15.1 ± 2.0 μg/mL, respectively. The concentrations of ciprofloxacin at 4 h and 12 h in ELF were 1.9 ± 0.9 μg/mL and 0.4 ± 0.1 μg/mL, respectively; AM concentrations were 34.9 ± 23.2 μg/mL and 6.8 ± 5.9 μg/mL, respectively. The differences in the ELF concentrations of the two levofloxacin groups vs those of the ciprofloxacin group were significant (p < 0.05) at each sampling time.

Conclusions: Levofloxacin was more extensively distributed into intrapulmonary compartments than ciprofloxacin and achieved significantly higher steady-state concentrations in plasma and ELF during the 24 h after drug administration.

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