Summary:
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 (Cmax) 5.04 ± 0.87 mg/L and 8.32 ± 0.64
mg/L; area under the concentration-time curve with extrapolation to infinity
(AUC0inf) 190.24 ± 29.23 mg h/L and 720.79 ± 75.57 mg h/L; elimination
half-time (tm) 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 Cmax/MIC and AUC024/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.
Keywords:
Levofloxacin, End stage renal failure, Haemodialysis, Pharmacokinetics
