Universität zu Köln

Westermann, Isabella, Gastine, Silke ORCID: 0000-0002-1069-6123, Mueller, Carsten, Rudolph, Wiebke, Peters, Frank, Bloos, Frank ORCID: 0000-0002-0767-7941, Pletz, Mathias and Hagel, Stefan ORCID: 0000-0003-2999-6131 (2021). 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. Br. J. Clin. Pharmacol., 87 (11). S. 4293 - 4304. HOBOKEN: WILEY. ISSN 1365-2125

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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 >= 4x 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Westermann, Isabella UNSPECIFIED UNSPECIFIED UNSPECIFIED Gastine, Silke UNSPECIFIED orcid.org/0000-0002-1069-6123 UNSPECIFIED Mueller, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudolph, Wiebke UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloos, Frank UNSPECIFIED orcid.org/0000-0002-0767-7941 UNSPECIFIED Pletz, Mathias UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagel, Stefan UNSPECIFIED orcid.org/0000-0003-2999-6131 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-582015
DOI:	10.1111/bcp.14846
Journal or Publication Title:	Br. J. Clin. Pharmacol.
Volume:	87
Number:	11
Page Range:	S. 4293 - 4304
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1365-2125
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CRITICALLY-ILL PATIENTS; CARLO DOSING SIMULATIONS; INTERMITTENT BOLUS; SEPTIC SHOCK; CLEARANCE; HEMOFILTRATION; ANTIBIOTICS Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58201