Population pharmacokinetics and probability of target attainment in patients with sepsis under renal replacement therapy receiving continuous infusion of meropenem: Sustained low-efficiency dialysis and continuous veno-venous haemodialysis.

Abstract

AIMS:

To describe the population pharmacokinetics (PK) and probability of target attainment (PTA) of continuous infusion (CI) of meropenem in septic patients receiving renal replacement therapy (RRT).

METHODS:

Fifteen patients without RRT, 13 patients receiving sustained low-efficiency dialysis and 12 patients receiving continuous veno-venous haemodialysis were included. Population PK analysis with Monte Carlo simulations for different dosing regimens was performed. For minimum inhibitory concentration 2 mg/L was chosen. The target was set as 50% time ≥4× minimum inhibitory concentration.

RESULTS:

The PK of meropenem was best described by a 1-compartment model with linear elimination. Serum creatinine, residual diuresis and time on RRT, with no difference between sustained low-efficiency dialysis and continuous veno-venous haemodialysis, were found to be significant covariates affecting clearance, explaining >20% of the clearance between subject variability. PTA analysis showed that in patients with RRT, 2 g/24 h, meropenem CI achieved a PTA of 95%. In patients without RRT, the target was achieved with 3 g/24 h CI or prolonged infusion of 1 g meropenem over 8 hours but not with bolus application of 1 g meropenem for 8 hours. Only 2 patients (both without RRT) had meropenem concentrations below the target level. However, approximately half of the patients with RRT receiving CI 3 g/24 h meropenem had toxic concentrations.

CONCLUSION:

We found relevant PK variability for meropenem CI in septic patients with or without RRT, leading to a substantial risk for overdosing in patients with RRT. This finding highlights the strong demand for personalized dosing in critically ill patients.

• Authors: Isabella Westermann, Silke Gastine, Carsten Müller, Wiebke Rudolph, Frank Peters, Frank Bloos, Mathias Pletz, Stefan Hagel
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 87 Issue 11 Pg. 4293-4303 (11 2021) ISSN: 1365-2125 [Electronic] England
• PMID: 33818823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Chemical References

• Anti-Bacterial Agents
• Meropenem

Topics

• Anti-Bacterial Agents (therapeutic use)
• Continuous Renal Replacement Therapy
• Humans
• Hybrid Renal Replacement Therapy
• Meropenem
• Probability
• Renal Replacement Therapy
• Sepsis (drug therapy)