Plasma Levels of Levofloxacin in Dialysis Patients After 500mg on Day 1
After a single 500mg dose of levofloxacin in hemodialysis patients, expect a peak plasma concentration (Cmax) of approximately 5.2 μg/mL occurring 1-2 hours post-dose, with trough levels around 2.7-2.9 μg/mL before the next dialysis session. 1
Peak and Trough Concentrations
Peak levels (Cmax): Following a 500mg intravenous dose administered after hemodialysis, median peak concentrations reach 5.2 μg/mL (range 4.1-11.3 μg/mL) within 1-2 hours 1
Trough levels: Before the next dialysis session (approximately 48 hours later), trough concentrations average 2.7 μg/mL (range 1.4-5.0 μg/mL) 1
Oral versus IV equivalence: Oral and intravenous levofloxacin achieve essentially identical plasma exposures at the same dose, with oral bioavailability approaching 100% 2, 1
Pharmacokinetic Parameters in ESRD
The pharmacokinetics of levofloxacin are dramatically altered in end-stage renal disease patients on hemodialysis compared to those with normal renal function:
Elimination half-life: Prolonged to 34.4 hours (range 28.4-39.3 hours) in hemodialysis patients versus 6-8 hours in normal renal function 1, 2
Systemic clearance: Reduced to 37.0 mL/min (range 12.8-42.7 mL/min) in ESRD patients 1
Volume of distribution: Approximately 103.3 L (range 39.8-139.3 L) or 1.1 L/kg, similar to patients with normal renal function 1, 2
Impact of Hemodialysis on Drug Removal
Dialytic clearance: Hemodialysis removes levofloxacin with a median clearance of 84.4 mL/min (range 61.8-107.6 mL/min) using a cellulose acetate high-performance dialyzer 1
Reduction ratio: Approximately 24.4% (range 18.1-41.2%) of levofloxacin is removed during a single hemodialysis session 1
Critical timing: Because approximately 80% of levofloxacin undergoes renal clearance, the drug is significantly removed by dialysis, making post-dialysis administration essential 3, 2
Therapeutic Adequacy
The 500mg dose on day 1 provides therapeutically adequate concentrations for most respiratory pathogens:
Cmax/MIC90 ratios ≥10: Achieved for Haemophilus influenzae, Moraxella catarrhalis, Enterobacter cloacae, and Klebsiella pneumoniae 1
Cmax/MIC90 ratio ~5: Achieved for Streptococcus pneumoniae 1
Inadequate coverage: Pseudomonas aeruginosa (Cmax/MIC90 <1) requires higher doses 1
Recommended Dosing Strategy
For hemodialysis patients, administer 500mg initially on day 1, followed by 250mg every 48 hours (or 750-1000mg three times weekly after each dialysis session for tuberculosis). 3, 4, 1
The loading dose of 500mg ensures adequate initial concentrations 1
Maintenance doses of 250mg every 48 hours prevent drug accumulation while maintaining therapeutic levels for organisms with MIC ≤1 μg/mL 1
For tuberculosis treatment specifically, higher doses of 750-1000mg three times weekly are recommended by the American Thoracic Society 3, 4, 5
Critical Pitfalls to Avoid
Never administer before dialysis: This results in premature drug removal and therapeutic failure 3, 4, 5
Avoid daily dosing: Daily administration leads to drug accumulation and increased neurotoxicity risk in dialysis patients 6, 5
Drug interactions: Do not administer within 2 hours of antacids or medications containing divalent cations (aluminum, magnesium, iron, calcium), as these dramatically reduce levofloxacin absorption 3, 6, 2
Monitoring Considerations
Therapeutic drug monitoring: Consider measuring serum concentrations at 2 and 6 hours post-dose to optimize dosing in patients with borderline renal function or multiple comorbidities 4, 6, 5
Neurotoxicity surveillance: Monitor for central nervous system toxicity, particularly in elderly patients, as this is a well-recognized complication in renal impairment 5