Sex-based pharmacokinetics of intravenous levofloxacin (LEV) in healthy subjects

Abstract

The influence of sex on the pharmacokinetics (PK) of IV LEV has not been well characterized, despite an apparent increased susceptibility of women to fluoroquinolone toxicity. PURPOSE To determine potential sex-based differences in the PK of LEV following systemic administration. METHODS Twenty healthy subjects (11M, 9F), received a single 500mg IV dose of LEV. Serum and urine were collected over 36 hr and LEV concentrations were determined by HPLC. A compartmental PK analysis was performed with ADAPT II and mean unadjusted and weight-adjusted parameter estimates were obtained. RESULTS The mean + SD weights were 75.1 + 11.8 and 63.3 + 10.3 kg for males and females, respectively (p=0.04). A 2 compartment model best fit the data; median (range) r2=0.996 (0.990–0.999). The PK analysis (see Table) revealed statistically significant differences in estimated PK parameters except t1/2. Weight-adjusted VSS for males and females were 1.59 + 0.11 and 1.28 + 0.15 L/kg, respectively (p<0.001). CONCLUSIONS Differences exist in LEV PK between males and females following IV administration. Fixed IV doses of LEV will lead to greater drug exposure in females. Clinical Pharmacology & Therapeutics (2004) 75, P66–P66; doi: 10.1016/j.clpt.2003.11.247 Table 1. Data presented as median (IQR) or mean + SD if normally distributed CLS† (L/hr) VC† (L) VSS† (L) CLR† (L/hr) Cmax† (mg/L) t1/2 (hr) Males 11.7 ± 2.1 55.0 ± 22.3 118.8 ± 17.7 10.2 ± 2.1 5.5 ± 0.5 7.3 (6.7, 8.3) Females 9.1 ± 1.1 30.2 ± 21.0 80.6 ± 12.7 7.2 ± 1.7 8.0 ± 2.6 6.4 (5.9, 7.1) † p < 0.05 based on t-test or nonparametric equivalent.