Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients—A Controlled Clinical Trial
| Autor: | Alexander Kratzer, Arne Dietrich, Felix Girrbach, Philipp Simon, Hermann Wrigge, Jana Heyne, Frieder Kees, David Petroff, Christoph Dorn, Markus Zeitlinger, Charlotte Kloft, David Busse |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_specialty obesity microdialysis 030106 microbiology Urology 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten 030226 pharmacology & pharmacy Biochemistry Microbiology Meropenem Article antibiotic dosing concentrations meropenem pharmacokinetics soft tissue pharmacodynamics 03 medical and health sciences 0302 clinical medicine Pharmacokinetics 615 Pharmazie Interstitial fluid medicine Pharmacology (medical) ddc:610 General Pharmacology Toxicology and Pharmaceutics Volume of distribution business.industry lcsh:RM1-950 Area under the curve ddc:615 Infectious Diseases medicine.anatomical_structure lcsh:Therapeutics. Pharmacology Pharmacodynamics business 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie Therapeutik Body mass index Subcutaneous tissue medicine.drug |
| Zdroj: | Antibiotics, Vol 9, Iss 931, p 931 (2020) Antibiotics Volume 9 Issue 12 |
| ISSN: | 2079-6382 |
| Popis: | 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) &ge 35 kg/m2) and age-/sex-matched nonobese (18.5 kg/m2 &ge BMI &le 30 kg/m2) 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/m2) and 15 nonobese (BMI 24 ± 2 kg/m2) patients were 54.0 vs. 63.9 mg/L (95% CI for difference: &minus 18.3 to &minus 3.5). The volume of distribution was 22.4 vs. 17.6 L, (2.6&ndash 9.1), but the clearance was comparable (12.5 vs. 11.1 L/h, &minus 1.4 to 3.1), leading to a longer half-life (1.52 vs. 1.31 h, 0.05&ndash 0.37) and fairly similar area under the curve (AUC)8h (78.7 vs. 89.2 mg*h/L, &minus 21.4 to 8.6). In the ISF, the maximum concentrations differed significantly (12.6 vs. 18.6 L, &minus 16.8 to &minus 0.8) but not the AUC8h (28.5 vs. 42.0 mg*h/L, &minus 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&ndash 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. |
| Databáze: | OpenAIRE |
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