Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Meropenem Disposition in Neonatal and Pediatric Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy

P. Pokorná, D. Michaličková, D. Tibboel, J. Berner

. 2024 ; 13 (5) : . [pub] 20240503

Status not-indexed Language English Country Switzerland

Document type Journal Article

Grant support
ISR Pfizer Grant 69506665 Pfizer
Institutional Program of Charles University in Prague (UNCE/MED/007) Charles University
Charles University project Cooperatio - Pediatric sciences Charles University
Charles University project Cooperatio - Pharmaceutical sciences Charles University

This study aimed to characterize the impact of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of meropenem in neonates and children and to provide recommendations for meropenem dosing in this specific population of patients. Therapeutic drug monitoring (152 meropenem plasma concentrations) data from 45 patients (38 received ECMO) with a body weight (BW) of 7.88 (3.62-11.97) kg (median (interquartile range)) and postnatal age of 3 (0-465) days were collected. The population PK analysis was performed using NONMEM V7.3.0. Monte Carlo simulations were performed to assess the probability of target achievement (PTA) for 40% of time the free drug remained above the minimum inhibitory concentration (fT > MIC) and 100% fT > MIC. BW was found to be a significant covariate for the volume of distribution (Vd) and clearance (CL). Additionally, continuous renal replacement therapy (CRRT) was associated with a two-fold increase in Vd. In the final model, the CL and Vd for a typical patient with a median BW of 7.88 kg that was off CRRT were 1.09 L/h (RSE = 8%) and 3.98 L (14%), respectively. ECMO did not affect meropenem PK, while superimposed CRRT significantly increased Vd. We concluded that current dosing regimens provide acceptably high PTA for MIC ≤ 4 mg/L for 40% fT > MIC, but individual dose adjustments are needed for 100% fT > MIC.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24012859
003      
CZ-PrNML
005      
20240726151430.0
007      
ta
008      
240723s2024 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/antibiotics13050419 $2 doi
035    __
$a (PubMed)38786147
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Pokorná, Pavla $u Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech Republic $u Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech Republic $u Department of Physiology and Pharmacology, Karolinska Institute and Karolinska University Hospital, 171 77 Stockholm, Sweden $u Department of Pediatric Surgery, Erasmus Medical Center Sophia Children's Hospital, 3062 PA Rotterdam, The Netherlands
245    10
$a Meropenem Disposition in Neonatal and Pediatric Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy / $c P. Pokorná, D. Michaličková, D. Tibboel, J. Berner
520    9_
$a This study aimed to characterize the impact of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of meropenem in neonates and children and to provide recommendations for meropenem dosing in this specific population of patients. Therapeutic drug monitoring (152 meropenem plasma concentrations) data from 45 patients (38 received ECMO) with a body weight (BW) of 7.88 (3.62-11.97) kg (median (interquartile range)) and postnatal age of 3 (0-465) days were collected. The population PK analysis was performed using NONMEM V7.3.0. Monte Carlo simulations were performed to assess the probability of target achievement (PTA) for 40% of time the free drug remained above the minimum inhibitory concentration (fT > MIC) and 100% fT > MIC. BW was found to be a significant covariate for the volume of distribution (Vd) and clearance (CL). Additionally, continuous renal replacement therapy (CRRT) was associated with a two-fold increase in Vd. In the final model, the CL and Vd for a typical patient with a median BW of 7.88 kg that was off CRRT were 1.09 L/h (RSE = 8%) and 3.98 L (14%), respectively. ECMO did not affect meropenem PK, while superimposed CRRT significantly increased Vd. We concluded that current dosing regimens provide acceptably high PTA for MIC ≤ 4 mg/L for 40% fT > MIC, but individual dose adjustments are needed for 100% fT > MIC.
590    __
$a NEINDEXOVÁNO
655    _2
$a časopisecké články $7 D016428
700    1_
$a Michaličková, Danica $u Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech Republic $1 https://orcid.org/0000000296909846
700    1_
$a Tibboel, Dick $u Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech Republic $u Department of Pediatric Surgery, Erasmus Medical Center Sophia Children's Hospital, 3062 PA Rotterdam, The Netherlands
700    1_
$a Berner, Jonas $u Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech Republic $u Department of Physiology and Pharmacology, Karolinska Institute and Karolinska University Hospital, 171 77 Stockholm, Sweden $u Pediatric Perioperative Medicine and Intensive Care, Astrid Lindgren Children's Hospital, Karolinska University Hospital, 171 76 Stockholm, Sweden $1 https://orcid.org/0000000212354776
773    0_
$w MED00195446 $t Antibiotics (Basel) $x 2079-6382 $g Roč. 13, č. 5 (2024)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38786147 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240723 $b ABA008
991    __
$a 20240726151423 $b ABA008
999    __
$a ok $b bmc $g 2125498 $s 1224722
BAS    __
$a 3
BAS    __
$a PreBMC-PubMed-not-MEDLINE
BMC    __
$a 2024 $b 13 $c 5 $e 20240503 $i 2079-6382 $m Antibiotics (Basel) $n Antibiotics (Basel) $x MED00195446
GRA    __
$a ISR Pfizer Grant 69506665 $p Pfizer
GRA    __
$a Institutional Program of Charles University in Prague (UNCE/MED/007) $p Charles University
GRA    __
$a Charles University project Cooperatio - Pediatric sciences $p Charles University
GRA    __
$a Charles University project Cooperatio - Pharmaceutical sciences $p Charles University
LZP    __
$a Pubmed-20240723

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...