Pharmacokinetics of levofloxacin during continuous veno-venous hemofiltration.
OBJECTIVE
To study the effect of continuous veno-venous hemofiltration (CVVHF) on the pharmacokinetics of levofloxacin in critically ill patients with acute renal failure.


METHODS
Open-label study.


METHODS
Anesthesiology ICU, University Hospital of Regensburg.


METHODS
Six critically ill patients treated with CVVHF because of acute renal failure needing antimicrobial therapy.


METHODS
Levofloxacin i.v. 250 mg qd with a starting dose of 500 mg. CVVHF with the following characteristics: hemofilter AN69 hollow fibers of 0.90 m2 area, blood flow 150 ml/min, ultrafiltrate flow 1.3 l/h, filtrate substitution in post-dilution mode.


RESULTS
The plasma pharmacokinetics and clearance of levofloxacin by hemofiltration were established on day 1 and day 4-6 of treatment. Levofloxacin was determined by high-performance liquid chromatography (HPLC). Mean (range) peak plasma concentrations after levofloxacin 500 mg single dose (s.d.) and 250 mg multiple dose (m.d.) were 6.4 (2.7-9.4) and 8.2 (4.7-10.3) mg/l, trough levels 2.7 (1.4-5.0) and 2.9 (1.7-3.9) mg/l, half-life 28 (19-38) and 22 (17-31) h, volume of distribution 1.2 (0.72-1.6) l/kg and 0.91 (0.52-2.0) l/kg, respectively. The mean sieving coefficient was 0.96 (0.79-1.09), mean total clearance 47 (20-89) ml/min, and mean clearance by hemofiltration 21 (13-27) ml/min, respectively.


CONCLUSIONS
A dosage schedule of levofloxacin 250 mg qd with a 500 mg loading dose seems appropriate for anuric patients during CVVHF. Sufficiently high steady-state concentrations of levofloxacin were achieved after the first dose. Undesired accumulation of levofloxacin was not observed.
Hansen
E
E
Intensive Care Unit, Clinic of Anesthesiology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. ernil.hansen@klinik.uni-regensburg.de
Bucher
M
M
Jakob
W
W
Lemberger
P
P
Kees
F
F
D058186:Acute Kidney Injury / Q000378:metabolism / Q000628:therapy*; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D016638:Critical Illness; D005260:Female; D006440:Hemofiltration / Q000379:methods*; D006801:Humans; D007362:Intensive Care Units; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018709:Statistics, Nonparametric
D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin