Pharmacokinetics of levofloxacin after single and multiple oral doses in patients undergoing intermittent haemodialysis

Abstract

The impact of intermittent haemodialysis (IHD) on the pharmacokinetics of levofloxacin after single and multiple oral doses of 500 mg was assessed in 10 patients with end-stage renal failure on IHD. In the first phase of the study where a single dose was administered, IHD was initiated 90 min after drug intake. In the second phase of the study where drug was administered daily for three consecutive days, IHD was started exactly after the first dose. Venous blood samples were collected at standard time intervals. Additional samples from the arterial and venous line of the fistula and from the dialysate were drawn at the first, second and fourth hour of the first IHD session. Levofloxacin concentrations were estimated by high performance liquid chromatography analysis using fluorescence detection. Median (±standard error) pharmacokinetic parameters after single and multiple dosing, respectively, were: maximum plasma concentration ( C max) 5.04 ± 0.87 mg/L and 8.32 ± 0.64 mg/L; area under the concentration–time curve with extrapolation to infinity (AUC 0→Inf) 190.24 ± 29.23 mg h/L and 720.79 ± 75.57 mg h/L; elimination half-time ( t 1/2) 22.84 ± 5.56 h and 38.05 ± 4.14 h; and clearance rate 2.67 ± 0.39 L/h and 2.10 ± 0.21 L/h. Removal of levofloxacin by IHD was indicated by a significant decrease in concentration from the arterial line to the venous line of the fistula. The C max/MIC and AUC 0→24/MIC ratios (where MIC is the minimum inhibitory concentration of the pathogen) remained above >100 and >10, respectively, rendering levofloxacin a candidate for infections in these patients.