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Pharmacokinetics and dosage adaptation of meropenem during continuous venovenous hemodiafiltration in critically ill

C Robatel1, L A Decosterd, J Biollaz

  • 1Division of Clinical Pharmacology, Department of Medicine, University Hospital, Lausanne, Switzerland.

Journal of Clinical Pharmacology
|November 15, 2003
PubMed

Insights

This study investigated meropenem (a broad-spectrum antibiotic) pharmacokinetics in patients undergoing continuous venovenous hemodiafiltration (CVVHDF). Optimized dosing regimens of 750 mg thrice daily or 1500 mg twice daily are recommended for effective treatment.

Area of Science:

  • Pharmacology
  • Nephrology
  • Infectious Diseases

Background:

  • Meropenem is a carbapenem antibiotic frequently used in patients requiring continuous venovenous hemodiafiltration (CVVHDF).
  • Understanding meropenem's disposition during CVVHDF is crucial for optimizing patient treatment and ensuring therapeutic efficacy.

Purpose of the Study:

  • To determine the pharmacokinetic profile of meropenem in patients undergoing CVVHDF.
  • To establish optimal meropenem dosing regimens for patients on CVVHDF.

Main Methods:

  • Pharmacokinetic analysis of meropenem in 15 patients on CVVHDF using high-performance liquid chromatography (HPLC).
  • Measurements of meropenem levels in plasma and filtrate-dialysate.
  • Noncompartmental and four-compartment modeling approaches were employed.

Main Results:

  • Mean total body clearance was 5.0 L/h, volume of distribution at steady state was 14.3 L, and mean residence time was 4.8 h.
  • Hemodiafiltration clearances were calculated as 1.2 L/h (plasma only) and 1.6 L/h (plasma with filtrate-dialysate).
  • The study identified two equally applicable therapeutic schedules: 750 mg thrice daily or 1500 mg twice daily.

Conclusions:

  • The pharmacokinetic data support specific meropenem dosing adjustments for patients on CVVHDF.
  • Optimized dosing ensures adequate drug exposure, considering the reference minimal inhibitory concentration (MIC) of 4 mg/L.

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