Simon, Philipp and Petroff, David and Busse, David and Heyne, Jana and Girrbach, Felix and Dietrich, Arne and Kratzer, Alexander and Zeitlinger, Markus and Kloft, Charlotte and Kees, Frieder and Wrigge, Hermann and Dorn, Christoph (2020) Meropenem Plasma and Interstitial Soft Tissue Concentrations in Obese and Nonobese Patients-A Controlled Clinical Trial. ANTIBIOTICS-BASEL, 9 (12): 931. ISSN 2079-6382,
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BETA-LACTAM ANTIBIOTICS; MORBIDLY OBESE; POPULATION PHARMACOKINETICS; HPLC; PHARMACODYNAMICS; PIPERACILLIN; PHARMACOLOGY; antibiotic dosing; concentrations; meropenem; microdialysis; obesity; pharmacokinetics; soft tissue; pharmacodynamics |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Frieder Kees |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Mar 2021 07:22 |
| Last Modified: | 08 Mar 2021 07:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43250 |
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