Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation
Limited studies have investigated population pharmacokinetic (PK) models and optimal dosage regimens of meropenem for critically ill adult patients using the probability of target attainment, including patients receiving extracorporeal membrane oxygenation (ECMO). A population PK analysis was conduc...
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| Online Access: | https://www.mdpi.com/1999-4923/13/11/1861 |
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| author | Dong-Hwan Lee Hyoung-Soo Kim Sunghoon Park Hwan-il Kim Sun-Hee Lee Yong-Kyun Kim |
| author_facet | Dong-Hwan Lee Hyoung-Soo Kim Sunghoon Park Hwan-il Kim Sun-Hee Lee Yong-Kyun Kim |
| author_sort | Dong-Hwan Lee |
| collection | DOAJ |
| description | Limited studies have investigated population pharmacokinetic (PK) models and optimal dosage regimens of meropenem for critically ill adult patients using the probability of target attainment, including patients receiving extracorporeal membrane oxygenation (ECMO). A population PK analysis was conducted using non-linear mixed-effect modeling. Monte Carlo simulation was used to determine for how long the free drug concentration was above the minimum inhibitory concentration (MIC) at steady state conditions in patients with various degrees of renal function. Meropenem PK in critically ill patients was described using a two-compartment model, in which glomerular filtration rate was identified as a covariate for clearance. ECMO did not affect meropenem PK. The simulation results showed that the current meropenem dosing regimen would be sufficient for attaining 40%<i>f</i>T<sub>>MIC</sub> for <i>Pseudomonas aeruginosa</i> at MIC ≤ 4 mg/L. Prolonged infusion over 3 h or a high-dosage regimen of 2 g/8 h was needed for MIC > 2 mg/L or in patients with augmented renal clearance, for a target of 100%<i>f</i>T<sub>>MIC</sub> or 100%<i>f</i>T<sub>>4XMIC</sub>. Our study suggests that clinicians should consider prolonged infusion or a high-dosage regimen of meropenem, particularly when treating critically ill patients with augmented renal clearance or those infected with pathogens with decreased in vitro susceptibility, regardless of ECMO support. |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T05:09:04Z |
| publishDate | 2021-11-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-8147efe6c5c14dfda55e26f5f711345d2023-11-23T00:58:46ZengMDPI AGPharmaceutics1999-49232021-11-011311186110.3390/pharmaceutics13111861Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane OxygenationDong-Hwan Lee0Hyoung-Soo Kim1Sunghoon Park2Hwan-il Kim3Sun-Hee Lee4Yong-Kyun Kim5Department of Clinical Pharmacology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14066, KoreaDepartment of Thoracic and Cardiovascular Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14066, KoreaDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14066, KoreaDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14066, KoreaDepartment of Thoracic and Cardiovascular Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14066, KoreaDivision of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14066, KoreaLimited studies have investigated population pharmacokinetic (PK) models and optimal dosage regimens of meropenem for critically ill adult patients using the probability of target attainment, including patients receiving extracorporeal membrane oxygenation (ECMO). A population PK analysis was conducted using non-linear mixed-effect modeling. Monte Carlo simulation was used to determine for how long the free drug concentration was above the minimum inhibitory concentration (MIC) at steady state conditions in patients with various degrees of renal function. Meropenem PK in critically ill patients was described using a two-compartment model, in which glomerular filtration rate was identified as a covariate for clearance. ECMO did not affect meropenem PK. The simulation results showed that the current meropenem dosing regimen would be sufficient for attaining 40%<i>f</i>T<sub>>MIC</sub> for <i>Pseudomonas aeruginosa</i> at MIC ≤ 4 mg/L. Prolonged infusion over 3 h or a high-dosage regimen of 2 g/8 h was needed for MIC > 2 mg/L or in patients with augmented renal clearance, for a target of 100%<i>f</i>T<sub>>MIC</sub> or 100%<i>f</i>T<sub>>4XMIC</sub>. Our study suggests that clinicians should consider prolonged infusion or a high-dosage regimen of meropenem, particularly when treating critically ill patients with augmented renal clearance or those infected with pathogens with decreased in vitro susceptibility, regardless of ECMO support.https://www.mdpi.com/1999-4923/13/11/1861meropenempopulation pharmacokineticscritically ill patientadultextracorporeal membrane oxygenationMonte Carlo simulation |
| spellingShingle | Dong-Hwan Lee Hyoung-Soo Kim Sunghoon Park Hwan-il Kim Sun-Hee Lee Yong-Kyun Kim Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation Pharmaceutics meropenem population pharmacokinetics critically ill patient adult extracorporeal membrane oxygenation Monte Carlo simulation |
| title | Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation |
| title_full | Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation |
| title_fullStr | Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation |
| title_full_unstemmed | Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation |
| title_short | Population Pharmacokinetics of Meropenem in Critically Ill Korean Patients and Effects of Extracorporeal Membrane Oxygenation |
| title_sort | population pharmacokinetics of meropenem in critically ill korean patients and effects of extracorporeal membrane oxygenation |
| topic | meropenem population pharmacokinetics critically ill patient adult extracorporeal membrane oxygenation Monte Carlo simulation |
| url | https://www.mdpi.com/1999-4923/13/11/1861 |
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