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Elimination of meropenem by continuous hemo(dia) filtration: an in vitro one-compartment model
T H Schroeder1, W A Krueger, M Hansen
1Department of Anaesthesiology, Eberhard-Karls-University Tuebingen, Germany. tschroeder@rics.bwh.harvard.edu
Abstract:
Meropenem is a carbapenem antibiotic with a wide spectrum of activity against most gram positive and gram negative bacteria including anaerobes. Dose adjustments are necessary during continuous renal replacement therapies of acute renal failure. This in vitro study was conducted to investigate the influence of different filter materials, surface areas (AN-69 0.6 m2 and 0.9 m2, polysulfone 0.75 m2, polyamide 0.6 m2), and increasing flow rates (from 3.3 - 26.7 ml/min) on the elimination of meropenem in an in vitro continuous hemo(dia)filtration model. Meropenem was measured using HPLC with UV-detection. While the clearance increased proportionally to increasing dialysate flow rates in filters with a surface area of 0.9 m2, a peak clearance was reached in the small filters at flow rates of 10.0 ml/min (polyamide 0.6 m2) and 18.3 ml/min (AN-69 0.6 m2), when tested under the same conditions. This indicated incomplete dialysate saturation due to the diminished time available for meropenem to equilibrate with the dialysate solution. No adsorption to either of the tested membranes was detected. Dosage recommendations derived from clinical studies might be appropriate when different filter materials, but similar operational settings of the continuous replacement therapy, are applied. Reduction of the recommended dose might be necessary, when renal replacement therapies with lower flow rates and/or filters with smaller surface areas are carried out.
Insights
Dose adjustments for meropenem during continuous renal replacement therapy depend on filter size and flow rate. Smaller filters and lower flow rates may necessitate reduced meropenem dosage due to incomplete drug equilibration.
Area of Science:
- Pharmacokinetics
- Nephrology
- Infectious Diseases
Background:
- Meropenem is a broad-spectrum carbapenem antibiotic crucial for treating various bacterial infections.
- Acute renal failure often requires continuous renal replacement therapies (CRRT), necessitating meropenem dose adjustments.
- Understanding meropenem elimination during CRRT is vital for maintaining therapeutic efficacy and preventing toxicity.
Purpose of the Study:
- To investigate the impact of different filter materials and surface areas on meropenem elimination during in vitro CRRT.
- To evaluate the influence of varying dialysate flow rates on meropenem clearance across different filter configurations.
- To provide data-driven insights for optimizing meropenem dosing in patients undergoing CRRT.
Main Methods:
- An in vitro continuous hemo(dia)filtration model was utilized.
- Experiments involved diverse filter materials (AN-69, polysulfone, polyamide) and surface areas (0.6 m², 0.75 m², 0.9 m²).
- Flow rates ranged from 3.3 to 26.7 ml/min, with meropenem concentrations measured by HPLC-UV.
Main Results:
- Meropenem clearance correlated with dialysate flow rates in larger filters (0.9 m²).
- Smaller filters (0.6 m²) exhibited peak clearance at specific flow rates (10.0-18.3 ml/min), indicating incomplete dialysate saturation.
- No significant meropenem adsorption to tested filter membranes was observed.
Conclusions:
- Meropenem elimination during CRRT is significantly influenced by filter surface area and dialysate flow rate.
- Current clinical dosage recommendations may suffice for CRRT with larger filters and similar settings.
- Reduced meropenem doses might be required for CRRT employing smaller filters or lower flow rates to ensure adequate drug levels.