Dorn, Christoph and Petroff, David and Neumann, Nancy and Kratzer, Alexander and El-Najjar, Nahed and Dietrich, Arne and Kloft, Charlotte and Zeitlinger, Markus and Kees, Martin G. and Kees, Frieder and Wrigge, Hermann and Simon, Philipp (2019) Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and non-obese surgical patients: a controlled clinical trial. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 74 (8). pp. 2335-2340. ISSN 0305-7453, 1460-2091
Full text not available from this repository. (Request a copy)Abstract
Objectives: To assess the pharmacokinetics and tissue penetration of fosfomycin in obese and non-obese surgical patients. Methods: 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. Results: Thirteen obese patients (BMI 38-50 kg/m(2)) and 14 non-obese patients (BMI 0-29 kg/m(2)) 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(infinity) 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(infinity) 1052 +/- 394 versus 1929 +/- 725 mg.h/L, P=0.0010). The tissue/plasma ratio (AUC(ISF)/AUC(plasma)) was 0.86 +/- 0.32 versus 1.27 +/- 0.34 (P=0.0047). Conclusions: 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TARGET SITE; PHARMACODYNAMICS; ANTIBIOTICS; PENETRATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 11:14 |
| Last Modified: | 01 Apr 2020 11:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26495 |
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