How do pharmacokinetics of vancomycin (generic name) change in a patient with end-stage renal disease (Impaired renal function) undergoing dialysis?

Vancomycin Pharmacokinetics in End-Stage Renal Disease with Dialysis

Fundamental Pharmacokinetic Alterations

In end-stage renal disease (ESRD) patients on dialysis, vancomycin's elimination half-life extends dramatically from 4-6 hours in normal renal function to approximately 7.5 days in anephric patients, fundamentally altering dosing requirements. 1

Volume of Distribution Changes

• The volume of distribution remains relatively preserved at 0.3-0.43 L/kg in ESRD patients, similar to those with normal renal function 1
• This means loading doses should still be weight-based at 25-30 mg/kg regardless of renal function, as volume of distribution is not affected by renal impairment 2
• Critically ill dialysis patients may have expanded extracellular volume from fluid resuscitation, potentially increasing the volume of distribution to 0.67-1.1 L/kg 3

Elimination and Clearance Alterations

• In patients with normal renal function, approximately 75% of vancomycin is excreted unchanged in urine within 24 hours via glomerular filtration 1
• Mean renal clearance drops from 0.048 L/kg/h in normal function to essentially zero in anephric patients 1
• The elimination half-life in the interdialytic period extends to approximately 101 ± 19 hours (roughly 4 days) 4
• Without dialysis removal, vancomycin would accumulate indefinitely in ESRD patients, as there is no apparent metabolism of the drug 1

Dialysis-Specific Removal Characteristics

High-Flux Hemodialysis Impact

• High-flux dialysis membranes significantly remove vancomycin, with clearance rates of 55.2 ± 18.5 ml/min during hemodialysis sessions 4
• A single hemodialysis session removes approximately 270 mg of vancomycin from the body 4
• When vancomycin is administered during the last hour of dialysis using high-flux membranes, 35% (range 18-56%) of the dose is removed during that session 5

Post-Dialysis Redistribution Phenomenon

• After hemodialysis completion, vancomycin redistributes from tissue compartments back into plasma, causing a rebound increase in serum concentrations 4
• The redistribution phenomenon accounts for approximately 10% increase in serum levels post-hemodialysis 4
• This rebound is less pronounced than with hemofiltration (which shows 25% redistribution) 4

Sustained Low-Efficiency Dialysis (SLED) Considerations

• SLED removes vancomycin more gradually over extended sessions (≥7 hours), reducing serum concentrations by 35.4% (31.5-43.8%) 3
• The vancomycin half-life during SLED is 13.6 hours (9.4-16.6 hours), significantly shorter than the interdialytic half-life 3
• Post-SLED rebound is minimal at only 9.8% (2.5-13.7%), requiring supplemental dosing after each SLED session 3
• Vancomycin clearance during SLED is 3.5 L/hr (2.2-5.2 L/hr) 3

Critical Dosing Implications

Loading Dose Strategy

• Always administer a weight-based loading dose of 20-25 mg/kg based on actual body weight, regardless of renal function or dialysis status 6, 2
• The loading dose is not affected by renal dysfunction because it depends on volume of distribution, not clearance 2
• Infuse loading doses over 2 hours to minimize infusion-related reactions 7

Maintenance Dosing Challenges

• Fixed-dose maintenance regimens fail to achieve target trough levels of 15-20 mg/L in the majority of hemodialysis patients 6
• Standard nomograms designed for patients with normal renal function will cause dangerous overdosing in ESRD patients 8
• The timing of administration (during versus after dialysis) dramatically affects drug removal and subsequent dosing requirements 6

Monitoring Requirements

• Trough monitoring is mandatory for all dialysis patients receiving vancomycin, with levels checked before the fourth dose and at least twice weekly throughout therapy 2, 8
• Target trough concentrations remain 15-20 mg/L for serious infections even in dialysis patients 2, 7
• Continuous therapeutic drug monitoring is essential due to the unpredictable interplay between prolonged interdialytic half-life and significant dialytic removal 9

Common Pitfalls to Avoid

• Never use conventional 1 g every 12 hours dosing in dialysis patients, as the prolonged half-life will cause toxic accumulation 8
• Never rely on standard dosing nomograms, as they were not designed for the extreme pharmacokinetic alterations in ESRD 8
• Never assume vancomycin is not removed by dialysis—high-flux membranes remove substantial amounts requiring post-dialysis supplementation 4, 5
• Never skip post-dialysis dosing when using high-flux membranes, as 35% of the dose is removed and minimal rebound occurs 5