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1000 Titel
  • Comparative Plasma and Interstitial Tissue Fluid Pharmacokinetics of Meropenem Demonstrate the Need for Increasing Dose and Infusion Duration in Obese and Non-obese Patients
1000 Autor/in
  1. Busse, David |
  2. Simon, Philipp |
  3. Schmitt, Lisa |
  4. Petroff, David |
  5. Dorn, Christoph |
  6. Dietrich, Arne |
  7. Zeitlinger, Markus |
  8. Huisinga, Wilhelm |
  9. Michelet, Robin |
  10. Wrigge, Hermann |
  11. Kloft, Charlotte |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-12-11
1000 Erschienen in
1000 Quellenangabe
  • 61(5):655-672
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s40262-021-01070-6 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095536/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background and objectives!#!A quantitative evaluation of the PK of meropenem, a broad-spectrum β-lactam antibiotic, in plasma and interstitial space fluid (ISF) of subcutaneous adipose tissue of obese patients is lacking as of date. The objective of this study was the characterisation of meropenem population pharmacokinetics in plasma and ISF in obese and non-obese patients for identification of adequate dosing regimens via Monte-Carlo simulations.!##!Methods!#!We obtained plasma and microdialysate concentrations after administration of meropenem 1000 mg to 15 obese and 15 non-obese surgery patients from a prospective clinical trial. After characterizing plasma- and microdialysis-derived ISF pharmacokinetics via population pharmacokinetic analysis, we simulated thrice-daily (TID) meropenem short-term (0.5 h), prolonged (3.0 h), and continuous infusions. Adequacy of therapy was assessed by the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) analysis based on time unbound concentrations exceeded minimum inhibitory concentrations (MIC) on treatment day 1 (%fT!##!Results!#!Adjusted body weight (ABW) and calculated creatinine clearance (CLCR!##!Conclusions!#!This analysis indicated a need for higher doses (≥ 2000 mg) and prolonged infusions (≥ 3 h) for obese and non-obese patients at MIC ≥ 2 mg/L. Higher PTA was achieved with prolonged infusions in obese patients and with continuous infusions in non-obese patients.!##!Trial registration!#!EudraCT: 2012-004383-22.
1000 Sacherschließung
lokal Meropenem/pharmacokinetics [MeSH]
lokal Pharmacology/Toxicology
lokal Anti-Bacterial Agents [MeSH]
lokal Humans [MeSH]
lokal Prospective Studies [MeSH]
lokal Original Research Article
lokal Obesity/drug therapy [MeSH]
lokal Internal Medicine
lokal Microbial Sensitivity Tests [MeSH]
lokal Monte Carlo Method [MeSH]
lokal Pharmacotherapy
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-2738-7797|https://orcid.org/0000-0003-2696-3254|https://frl.publisso.de/adhoc/uri/U2NobWl0dCwgIExpc2E=|https://orcid.org/0000-0002-6916-1465|https://orcid.org/0000-0002-2560-9598|https://frl.publisso.de/adhoc/uri/RGlldHJpY2gsICBBcm5lIA==|https://frl.publisso.de/adhoc/uri/WmVpdGxpbmdlciwgIE1hcmt1cw==|https://frl.publisso.de/adhoc/uri/SHVpc2luZ2EsICBXaWxoZWxt|https://orcid.org/0000-0002-5485-607X|https://orcid.org/0000-0002-9035-6822|https://frl.publisso.de/adhoc/uri/S2xvZnQsIENoYXJsb3R0ZQ==
1000 Hinweis
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1000 Erstellt am 2023-11-16T08:39:23.205+0100
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