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Article

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

1
Department of Pharmaceutical Medicine and Regulatory Science, Yonsei University, Incheon 21983, Korea
2
Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea
3
Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea
4
Department of Regulatory Science, College of Pharmacy, Graduate School, Kyung Hee University, Seoul 02447, Korea
5
School of Pharmacy, Jeonbuk National University, Jeonju 54896, Korea
6
Division of Cardiology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Korea
7
Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
8
Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon 21983, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2022, 11(22), 6621; https://doi.org/10.3390/jcm11226621
Submission received: 10 October 2022 / Revised: 23 October 2022 / Accepted: 2 November 2022 / Published: 8 November 2022
(This article belongs to the Special Issue Infection, Super Infection and Antimicrobial Management in ICU)

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.
Keywords: meropenem; extracorporeal membrane oxygenation; ECMO; dosage optimization; population pharmacokinetics meropenem; extracorporeal membrane oxygenation; ECMO; dosage optimization; population pharmacokinetics

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MDPI and ACS Style

Kang, S.; Yang, S.; Hahn, J.; Jang, J.Y.; Min, K.L.; Wi, J.; Chang, M.J. Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling. J. Clin. Med. 2022, 11, 6621. https://doi.org/10.3390/jcm11226621

AMA Style

Kang S, Yang S, Hahn J, Jang JY, Min KL, Wi J, Chang MJ. Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling. Journal of Clinical Medicine. 2022; 11(22):6621. https://doi.org/10.3390/jcm11226621

Chicago/Turabian Style

Kang, Soyoung, Seungwon Yang, Jongsung Hahn, June Young Jang, Kyoung Lok Min, Jin Wi, and Min Jung Chang. 2022. "Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling" Journal of Clinical Medicine 11, no. 22: 6621. https://doi.org/10.3390/jcm11226621

APA Style

Kang, S., Yang, S., Hahn, J., Jang, J. Y., Min, K. L., Wi, J., & Chang, M. J. (2022). Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling. Journal of Clinical Medicine, 11(22), 6621. https://doi.org/10.3390/jcm11226621

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