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Simon, Philipp ; Petroff, David ; Busse, David ; Heyne, Jana ; Girrbach, Felix ; Dietrich, Arne ; Kratzer, Alexander Ludwig ; Zeitlinger, Markus ; Kloft, Charlotte ; Kees, Frieder ; Wrigge, Hermann ; Dorn, Christoph

Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial

Simon, Philipp, Petroff, David, Busse, David , Heyne, Jana, Girrbach, Felix, Dietrich, Arne, Kratzer, Alexander Ludwig, Zeitlinger, Markus, Kloft, Charlotte, Kees, Frieder, Wrigge, Hermann und Dorn, Christoph (2020) Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial. Antibiotics 9 (12), S. 931.

Veröffentlichungsdatum dieses Volltextes: 11 Jan 2021 05:57
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.44376


Zusammenfassung

Background: This controlled clinical study aimed to investigate the impact of obesity on plasma and tissue pharmacokinetics of meropenem. Methods: Obese (body mass index (BMI) >= 35 kg/m(2)) and age-/sex-matched nonobese (18.5 kg/m(2) >= BMI <= 30 kg/m(2)) surgical patients received a short-term infusion of 1000-mg meropenem. Concentrations were determined via high performance liquid ...

Background: This controlled clinical study aimed to investigate the impact of obesity on plasma and tissue pharmacokinetics of meropenem. Methods: Obese (body mass index (BMI) >= 35 kg/m(2)) and age-/sex-matched nonobese (18.5 kg/m(2) >= BMI <= 30 kg/m(2)) surgical patients received a short-term infusion of 1000-mg meropenem. Concentrations were determined via high performance liquid chromatography-ultraviolet (HPLC-UV) in the plasma and microdialysate from the interstitial fluid (ISF) of subcutaneous tissue up to eight h after dosing. An analysis was performed in the plasma and ISF by noncompartmental methods. Results: The maximum plasma concentrations in 15 obese (BMI 49 +/- 11 kg/m(2)) and 15 nonobese (BMI 24 +/- 2 kg/m(2)) patients were 54.0 vs. 63.9 mg/L (95% CI for difference: -18.3 to -3.5). The volume of distribution was 22.4 vs. 17.6 L, (2.6-9.1), but the clearance was comparable (12.5 vs. 11.1 L/h, -1.4 to 3.1), leading to a longer half-life (1.52 vs. 1.31 h, 0.05-0.37) and fairly similar area under the curve (AUC)(8h) (78.7 vs. 89.2 mg*h/L, -21.4 to 8.6). In the ISF, the maximum concentrations differed significantly (12.6 vs. 18.6 L, -16.8 to -0.8) but not the AUC(8h) (28.5 vs. 42.0 mg*h/L, -33.9 to 5.4). Time above the MIC (T > MIC) in the plasma and ISF did not differ significantly for MICs of 0.25-8 mg/L. Conclusions: In morbidly obese patients, meropenem has lower maximum concentrations and higher volumes of distribution. However, due to the slightly longer half-life, obesity has no influence on the T > MIC, so dose adjustments for obesity seem unnecessary.



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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftAntibiotics
Verlag:MDPI
Ort der Veröffentlichung:BASEL
Band:9
Nummer des Zeitschriftenheftes oder des Kapitels:12
Seitenbereich:S. 931
Datum2020
InstitutionenChemie und Pharmazie > Institut für Pharmazie > Arbeitsgruppe Klinische Pharmazie (Dr. Dorn)
Chemie und Pharmazie > Institut für Pharmazie > Entpflichtete oder im Ruhestand befindliche Professoren > Prof. Wiegrebe
Identifikationsnummer
WertTyp
10.3390/antibiotics9120931DOI
Stichwörter / KeywordsBETA-LACTAM ANTIBIOTICS; MORBIDLY OBESE; POPULATION PHARMACOKINETICS; HPLC; PHARMACODYNAMICS; PIPERACILLIN; PHARMACOLOGY; antibiotic dosing; concentrations; meropenem; microdialysis; obesity; pharmacokinetics; soft tissue; pharmacodynamics
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 615 Pharmazie
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-443760
Dokumenten-ID44376

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