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Pharmacokinetics of meropenem in critically ill patients with acute renal failure undergoing continuous venovenous
I Tegeder1, F Neumann, F Bremer
1Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Objective:
Meropenem is a broad-spectrum antibiotic used for severe infections. In patients with chronic end-stage renal failure, meropenem clearance is reduced and doses must be adjusted according to the creatinine clearance. The aim of this study was to assess pharmacokinetic data of meropenem in patients with acute renal failure and to determine the amount of drug removed by continuous venovenous hemofiltration, an often-used renal replacement therapy in patients with acute renal failure.
Methods:
Nine critically ill anuric patients with acute renal failure undergoing continuous venovenous hemofiltration received 500 mg meropenem 2 or 3 times daily. Plasma and hemofiltrate concentrations were determined during 1 dosing interval at steady state. Pharmacokinetic parameters were calculated for a 2-compartment open model and dose requirements were calculated.
Results:
The total meropenem clearance was 52.0 +/- 8.4 mL/min, with a hemofiltration clearance of 22.0 +/- 4.7 mL/min and a nonrenal-nonhemofiltration clearance of 29.9 +/- 5.4 mL/min; 235.9 +/- 88.6 mg, or 47.2% +/- 17.7%, of the dose were removed through continuous venovenous hemofiltration. The terminal elimination half-life was 8.7 +/- 3.5 hours and the volume of distribution at steady state was 12.4 +/- 1.8 L. Peak and trough concentrations for a dosing interval of 12 hours were 38.9 +/- 9.7 mg/L and 7.3 +/- 1.3 mg/L, respectively. The corresponding concentrations for a dosing interval of 8 hours were 44.7 +/- 10.4 mg/L and 11.9 +/- 0.7 mg/L, respectively.
Conclusion:
Pharmacokinetic data of anuric patients with acute renal failure were similar to those of patients with end-stage renal failure. Because hemofiltration contributes significantly to meropenem elimination, the recommended dose for critically ill anuric patients receiving continuous venovenous hemofiltration should be increased by 100% to avoid potential underdosing.
Insights
Meropenem clearance is reduced in patients with acute renal failure undergoing continuous venovenous hemofiltration. Doses should be doubled to avoid underdosing in these critically ill patients.
Area of Science:
- Pharmacokinetics and drug dosing in critical care settings.
- Renal replacement therapy and drug elimination.
- Antibiotic management in acute kidney injury.
Background:
- Meropenem is a vital broad-spectrum antibiotic for severe infections.
- Renal impairment significantly affects meropenem clearance, necessitating dose adjustments.
- Continuous venovenous hemofiltration (CVVH) is common in acute renal failure (ARF).
Purpose of the Study:
- To evaluate meropenem pharmacokinetics in critically ill patients with ARF undergoing CVVH.
- To quantify meropenem removal by CVVH.
- To establish optimal meropenem dosing regimens for patients on CVVH.
Main Methods:
- Nine anuric ARF patients on CVVH received 500 mg meropenem 2-3 times daily.
- Plasma and hemofiltrate meropenem concentrations were measured at steady state.
- Pharmacokinetic parameters were calculated using a 2-compartment model.
Main Results:
- Total meropenem clearance was 52.0 mL/min; CVVH cleared 22.0 mL/min (47.2% of the dose).
- Terminal elimination half-life was 8.7 hours; volume of distribution was 12.4 L.
- Peak and trough concentrations varied based on dosing intervals (8 or 12 hours).
Conclusions:
- Meropenem pharmacokinetics in ARF patients on CVVH resemble those with end-stage renal failure.
- CVVH significantly contributes to meropenem elimination.
- A 100% dose increase is recommended for meropenem in critically ill anuric patients on CVVH to prevent underdosing.