Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and non-obese surgical patients: a controlled clinical trial

• Published in: Journal of antimicrobial chemotherapy Vol. 74; no. 8; pp. 2335 - 2340
• Main 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
• Format: Journal Article
• Language: English
• Published: England 01-08-2019
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkz203

To assess the pharmacokinetics and tissue penetration of fosfomycin in obese and non-obese surgical patients.
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.
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).
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.