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- Title
Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and non-obese surgical patients: a controlled clinical trial.
- Authors
Dorn, Christoph; Petroff, David; Neumann, Nancy; Kratzer, Alexander; El-Najjar, Nahed; Dietrich, Arne; Kloft, Charlotte; Zeitlinger, Markus; Kees, Martin G; Kees, Frieder; Wrigge, Hermann; Simon, Philipp
- Abstract
<bold>Objectives: </bold>To assess the pharmacokinetics and tissue penetration of fosfomycin in obese and non-obese surgical patients.<bold>Methods: </bold>Fifteen obese patients undergoing bariatric surgery and 15 non-obese patients undergoing major intra-abdominal surgery received an intravenous single short infusion of 8 g of fosfomycin. Fosfomycin concentrations were determined by LC-MS/MS in plasma and microdialysate from subcutaneous tissue up to 8 h after dosing. The pharmacokinetic analysis was performed in plasma and interstitial fluid (ISF) by non-compartmental methods.<bold>Results: </bold>Thirteen obese patients (BMI 38-50 kg/m2) and 14 non-obese patients (BMI 0-29 kg/m2) were evaluable. The pharmacokinetics of fosfomycin in obese versus non-obese patients were characterized by lower peak plasma concentrations (468 ± 139 versus 594 ± 149 mg/L, P = 0.040) and higher V (24.4 ± 6.4 versus 19.0 ± 3.1 L, P = 0.010). The differences in AUC∞ were not significant (1275 ± 477 versus 1515 ± 352 mg·h/L, P = 0.16). The peak concentrations in subcutaneous tissue were reached rapidly and declined in parallel with the plasma concentrations. The drug exposure in tissue was nearly halved in obese compared with non-obese patients (AUC∞ 1052 ± 394 versus 1929 ± 725 mg·h/L, P = 0.0010). The tissue/plasma ratio (AUCISF/AUCplasma) was 0.86 ± 0.32 versus 1.27 ± 0.34 (P = 0.0047).<bold>Conclusions: </bold>Whereas the pharmacokinetics of fosfomycin in plasma of surgical patients were only marginally different between obese and non-obese patients, the drug exposure in subcutaneous tissue was significantly lower in the obese patients.
- Subjects
PHARMACOKINETICS; CLINICAL trials; FAT cells; EXTRACELLULAR fluid; BARIATRIC surgery
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2019, Vol 74, Issue 8, p2335
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkz203