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Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling

Authors
 Soyoung Kang  ;  Seungwon Yang  ;  Jongsung Hahn  ;  June Young Jang  ;  Kyoung Lok Min  ;  Jin Wi  ;  Min Jung Chang 
Citation
 JOURNAL OF CLINICAL MEDICINE, Vol.11(22) : 6621, 2022-11 
Journal Title
JOURNAL OF CLINICAL MEDICINE
Issue Date
2022-11
Keywords
ECMO ; dosage optimization ; extracorporeal membrane oxygenation ; meropenem ; population pharmacokinetics
Abstract
Background: Our objective was to determine an optimal dosage regimen of meropenem in patients receiving veno-arterial extracorporeal membrane oxygenation (V-A ECMO) by developing a pharmacokinetic/pharmacodynamic (PK/PD) model. Methods: This was a prospective cohort study. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF). The population pharmacokinetic model was developed using nonlinear mixed-effects modeling. A Monte Carlo simulation was used (n = 10,000) to assess the probability of target attainment. Results: Thirteen adult patients on ECMO receiving meropenem were included. Meropenem pharmacokinetics was best fitted by a two-compartment model. The final pharmacokinetic model was: CL (L/h) = 3.79 × 0.44CRRT, central volume of distribution (L) = 2.4, peripheral volume of distribution (L) = 8.56, and intercompartmental clearance (L/h) = 21.3. According to the simulation results, if more aggressive treatment is needed (100% fT > MIC target), dose increment or extended infusion is recommended. Conclusions: We established a population pharmacokinetic model for meropenem in patients receiving V-A ECMO and revealed that it is not necessary to adjust the dosage depending on V-A ECMO. Instead, more aggressive treatment is needed than that of standard treatment, and higher dosage is required without continuous renal replacement therapy (CRRT). Also, extended infusion could lead to better target attainment, and we could provide updated nomograms of the meropenem dosage regimen.
Files in This Item:
T9992023109.pdf Download
DOI
10.3390/jcm11226621
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Wi, Jin(위진) ORCID logo https://orcid.org/0000-0003-0655-5130
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/194451
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