Meropenem Population Pharmacokinetics and Dosing Regimen Optimization in Critically Ill Children Receiving Continuous Renal Replacement Therapy

Background and Objective We aimed to develop a meropenem population pharmacokinetic model in critically ill children receiving continuous renal replacement therapy and simulate dosing regimens to optimize patient exposure. Methods Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem pharmacokinetics was investigated using a non-linear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration, according to the target of a 100% inter-dose interval time in which concentration is one to four times above the minimum inhibitory concentration (100% fT>1–4×MIC). Results A total of 27 patients with a median age of 4 [interquartile range 0–11] years, a median body weight of 16 [range 7–35] kg receiving continuous renal replacement therapy were included. Concentration–time courses were best described by a one-compartment model with first-order elimination. Body weight (BW) produced significant effects on volume of distribution (V) and BW and continuous renal replacement therapy effluent flow rate (Qeff) produced significant effects on clearance (CL): $${V}_{i}={V}_{pop }{x (\frac{BWi}{70})}^{1}$$ and $${CL}_{i}={CL}_{pop }x ({\frac{BWi}{70})}^{0.75} x ({\frac{Qeffi}{1200})}^{0.337}$$, where $ V_{pop} $ and $ CL_{pop} $ estimates were 32.5 L and 5.88 L/h, respectively, normalized to a 70-kg BW and median Qeff at 1200 mL/h. Using this final model and Monte Carlo simulations, for patients with Qeff over 1200 mL/h, meropenem continuous infusion was adequate in most cases to attain 100% fT>1–4xMIC. For bacterial infections with a low minimum inhibitory concentration (≤2 mg/L), meropenem intermitent administration was appropriate for patients weighing more than 20 kg with Qeff <500 mL/h and for patients weighing more than 10 kg with Qeff <100 mL/h. Conclusions Meropenem exposure in critically ill children receiving continuous renal replacement therapy needs dosing adjustments to the minimum inhibitory concentration that take into account body weight and the continuous renal replacement therapy effluent flow rate..

Medienart:	E-Artikel

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	Zur Gesamtaufnahme - volume:61
Enthalten in:	Clinical pharmacokinetics - 61(2022), 11 vom: 17. Okt., Seite 1609-1621

Sprache:	Englisch

Beteiligte Personen:

Thy, Michael [VerfasserIn] Urien, Saik [VerfasserIn] Bouazza, Naim [VerfasserIn] Foissac, Frantz [VerfasserIn] Gana, Inès [VerfasserIn] Bille, Emmanuelle [VerfasserIn] Béranger, Agathe [VerfasserIn] Toubiana, Julie [VerfasserIn] Berthaud, Romain [VerfasserIn] Lesage, Fabrice [VerfasserIn] Renolleau, Sylvain [VerfasserIn] Tréluyer, Jean-Marc [VerfasserIn] Benaboud, Sihem [VerfasserIn] Oualha, Mehdi [VerfasserIn]

Links:	Volltext [lizenzpflichtig]

Anmerkungen:	© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:	10.1007/s40262-022-01179-2

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC2132698414