Levofloxacin pharmacokinetics in ESRD and removal by the cellulose acetate high performance-210 hemodialyzer.
BACKGROUND
No published data are available describing the pharmacokinetics of intravenous levofloxacin in patients with end-stage renal disease (ESRD). Objectives of this study are to determine the pharmacokinetics and dialytic clearance of levofloxacin and develop dosing strategies in these patients.


METHODS
Eight noninfected subjects receiving long-term thrice-weekly hemodialysis, with no measurable residual renal function, were administered intravenous levofloxacin, 250 mg, over 1 hour after a scheduled hemodialysis session. Blood samples were collected serially during the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum concentrations of levofloxacin were determined by high-performance liquid chromatography. Differential equations describing a 2-compartment open-infusion pharmacokinetic model were fit to each individual subject's serum concentration-time data by iterative nonlinear weighted least-squares regression analysis using Adapt II (Biomedical Simulations Resource, University of Southern California, Los Angeles, CA). Ratios of maximum serum concentration (C(max)) to minimum inhibitory concentration (MIC) were calculated for common respiratory pathogens by using MIC for 90% of isolates (MIC90) data from published studies.


RESULTS
All subjects completed the study, and no adverse events were reported. Median systemic clearance, volume of distribution at steady state, elimination half-life, and C(max) were 37.0 mL/min (range, 12.8 to 42.7 mL/min), 103.3 L (range, 39.8 to 139.3 L), 34.4 hours (range, 28.4 to 39.3 hours), and 5.2 microg/mL (range, 4.1 to 11.3 microg/mL), respectively. Median dialytic clearance and levofloxacin reduction ratios were 84.4 mL/min (range, 61.8 to 107.6 mL/min) and 0.244 (range, 0.181 to 0.412), respectively. Median C(max)-MIC90 ratios were 10 or greater for Haemophilus influenzae, Moraxella catarrhalis, Enterobacter cloacae, and Klebsiella pneumoniae, approximately 5 for Streptococcus pneumoniae, and less than 1 for Pseudomonas aeruginosa.


CONCLUSIONS
The administration of levofloxacin to patients with ESRD as 500 mg initially, followed by 250 mg every 48 hours, will provide adequate C(max)-MIC ratios after the first and subsequent doses for most patients with respiratory tract infections caused by organisms with levofloxacin MICs of 1 microg/mL or less.
Sowinski
Kevin M
KM
Department of Pharmacy Practice, School of Pharmacy and Pharmacal Sciences, Purdue University, Indianapolis, IN 46202-2879, USA. ksowinsk@iupui.edu
Lucksiri
Aroonrut
A
Kays
Michael B
MB
Scott
Meri K
MK
Mueller
Bruce A
BA
Hamburger
Richard J
RJ
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D002482:Cellulose / Q000031:analogs & derivatives*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000628:therapy; D064704:Levofloxacin; D008297:Male; D008567:Membranes, Artificial; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006435:Renal Dialysis / Q000295:instrumentation*; D012141:Respiratory Tract Infections / Q000150:complications / Q000188:drug therapy / Q000382:microbiology
D000890:Anti-Infective Agents; D008567:Membranes, Artificial; C005062:acetylcellulose; D064704:Levofloxacin; D002482:Cellulose; D015242:Ofloxacin