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Original Research: INFECTIONS |

Levofloxacin Pharmacokinetics in Adult Cystic Fibrosis*

Carlton K. K. Lee, PharmD, MPH; Michael P. Boyle, MD, FCCP; Marie Diener-West, PhD; Lois Brass-Ernst, RN; Michelle Noschese, MS, CRNP; Pamela L. Zeitlin, MD, PhD, FCCP
Author and Funding Information

*From the Departments of Pediatrics (Drs. Lee and Zeitlin, and Ms. Brass-Ernst) and Medicine (Dr. Boyle and Ms. Noschese), Johns Hopkins University; and Department of Biostatistics (Dr. Diener-West), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.

Correspondence to: Carlton K. K. Lee, PharmD, MPH, Assistant Professor, Pediatrics, Pediatric Infectious Diseases, Johns Hopkins University, 600 North Wolfe St, Carnegie 180, Baltimore, MD 21287-6180; e-mail: cleea@jhmi.edu



Chest. 2007;131(3):796-802. doi:10.1378/chest.06-1524
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Background: Cystic fibrosis (CF) patients have enhanced renal clearance of aminoglycosides and several β-lactams and require higher dosages. Levofloxacin is a fluoroquinolone with extensive renal elimination and enhanced penetration into lungs and Pseudomonas aeruginosa (PA) biofilms. We studied the preliminary pharmacokinetic and pharmacodynamic (PK/PD) relationship of levofloxacin in CF.

Methods: Twelve patients at least 18 years old with a mild-to-moderate pulmonary exacerbation and fluoroquinolone-sensitive PA colonization received oral levofloxacin, 500 mg qd, for 14 days. Steady-state serum concentrations were collected after 3 to 7 days, and sputum samples for PA densities were collected before and after levofloxacin. PK/PD relationships for reducing PA sputum densities were evaluated.

Results: When compared to published data on non-CF patients, CF patients had similar area under the curve for 24 h (AUC24), total clearance, volume of distribution, maximum serum concentration (Cpmax), and elimination half-life: mean, 7.33 μg × h/mL/kg (SD, 1.70); 2.43 mL/min/kg (SD, 0.74); 1.33 L/kg (SD, 0.37); 7.06 μg/mL (SD, 2.35); and 6.44 h (SD, 1.1), respectively. Time to reach maximum serum concentration (Tmax) in CF was longer: mean, 2.20 h (SD, 0.99) vs 1.1 h (SD, 0.4) [p < 0.01]. Preliminary PK/PD analysis failed to demonstrate trends for decreasing PA sputum densities with increasing Cpmax/minimum inhibitory concentration (MIC) ratio and AUC24/MIC ratio.

Conclusion: CF levofloxacin pharmacokinetics corrected for body weight are similar to non-CF, except for Tmax. Standard levofloxacin dosing (especially monotherapy) is unlikely to produce maximum therapeutic effectiveness. Additional levofloxacin studies in CF are necessary to evaluate its sputum concentrations; the benefits of higher daily dosages (≥ 750 mg); and establish PK/PD targets for managing PA pulmonary infections.

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