STUDY OBJECTIVE: To characterize and compare the pharmacokinetics of levofloxacin in men and women after systemic administration. DESIGN: Prospective, open-label, parallel group pharmacokinetic study. SETTING: University research center. SUBJECTS: Eleven healthy men and nine healthy women stratified by body mass index. INTERVENTION: Subjects received levofloxacin as a single 500-mg intravenous dose. Serum and urine were collected over 36 hours. MEASUREMENTS AND MAIN RESULTS: Levofloxacin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic analysis was performed with ADAPT II software (University of Southern California, Los Angeles, CA). Median (range) body mass index was 23.2 kg/m2 (19.9-28.3 kg/m2) for men and 23.6 kg/m2 (16.0-32.4 kg/m2) for women (p = 0.67). A two-compartment model best fit the pharmacokinetic data: median (range) R2 was 0.996 (0.990-0.999). Women had a 24% greater exposure to levofloxacin, with a significantly smaller steady-state volume of distribution (p < 0.01) and a slower clearance (p < 0.01). CONCLUSIONS: Differences exist in the disposition of levofloxacin between healthy men and women after systemic administration. Fixed intravenous doses of levofloxacin will lead to greater drug exposure in women. Thus, women may have more of an increased risk of fluoroquinolone toxicity than men, and men may need higher doses to achieve similar drug efficacy than women. Levofloxacin dosage adjustments based on sex should be considered on an individual basis.
STUDY OBJECTIVE: To characterize and compare the pharmacokinetics of levofloxacin in men and women after systemic administration. DESIGN: Prospective, open-label, parallel group pharmacokinetic study. SETTING: University research center. SUBJECTS: Eleven healthy men and nine healthy women stratified by body mass index. INTERVENTION: Subjects received levofloxacin as a single 500-mg intravenous dose. Serum and urine were collected over 36 hours. MEASUREMENTS AND MAIN RESULTS:Levofloxacin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic analysis was performed with ADAPT II software (University of Southern California, Los Angeles, CA). Median (range) body mass index was 23.2 kg/m2 (19.9-28.3 kg/m2) for men and 23.6 kg/m2 (16.0-32.4 kg/m2) for women (p = 0.67). A two-compartment model best fit the pharmacokinetic data: median (range) R2 was 0.996 (0.990-0.999). Women had a 24% greater exposure to levofloxacin, with a significantly smaller steady-state volume of distribution (p < 0.01) and a slower clearance (p < 0.01). CONCLUSIONS: Differences exist in the disposition of levofloxacin between healthy men and women after systemic administration. Fixed intravenous doses of levofloxacin will lead to greater drug exposure in women. Thus, women may have more of an increased risk of fluoroquinolonetoxicity than men, and men may need higher doses to achieve similar drug efficacy than women. Levofloxacin dosage adjustments based on sex should be considered on an individual basis.