Sanz-Codina, Maria and van Os, Wisse and Pham, Anh Duc and Jorda, Anselm and Woelf-Duchek, Michael and Bergmann, Felix and Lackner, Edith and Lier, Constantin and Coen van Hasselt, J. G. and Minichmayr, Iris K. and Dorn, Christoph and Zeitlinger, Markus and al Jalali, Valentin (2024) Target-site cefiderocol pharmacokinetics in soft tissues of healthy volunteers. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 79 (12). pp. 3281-3288. ISSN 0305-7453, 1460-2091
Full text not available from this repository. (Request a copy)Abstract
Background Cefiderocol may potentially be used to treat skin and soft tissue infections (SSTIs). However, the pharmacokinetics of cefiderocol in human soft tissues have not yet been determined. The objective of the present PK study was to investigate whether target-site concentrations of cefiderocol are sufficiently high for the treatment of SSTIs.Methods In this pharmacokinetic study, a single intravenous dose of 2 g cefiderocol was administered to eight healthy male volunteers. Drug concentrations were determined in plasma, muscle and subcutis over 8 h. Free plasma concentrations were calculated using the plasma protein binding determined with ultrafiltration. Free tissue concentrations were obtained using microdialysis. Penetration ratios were calculated as AUC0-8h_free_tissue/AUC0-8h_free_plasma. A population pharmacokinetic model was developed, and the probability of target attainment (PTA) was determined using Monte Carlo simulations.Results Cefiderocol showed good tissue penetration, with mean penetration ratios +/- standard deviation of 0.99 +/- 0.33 and 0.92 +/- 0.30 for subcutis and muscle, respectively. Cefiderocol pharmacokinetics in plasma were best described with a two-compartment model, and tissue concentrations were described by scaling the tissue concentrations to concentrations in the peripheral compartment of the plasma model. For a thrice-daily regimen with 2 g doses intravenously infused over 3 h, PTA was >= 90% for MIC values up to 4 mg/L, both based on free plasma and soft tissue pharmacokinetics.Conclusions This study indicates that a dose of 2 g cefiderocol achieves concentrations in plasma considered sufficient for treating relevant bacterial species. Assuming a comparable PK/PD target for soft tissues, sufficiently high concentrations would also be achieved in soft tissues.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MICRODIALYSIS; SKIN; MODEL |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jan 2026 10:37 |
| Last Modified: | 22 Jan 2026 10:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64784 |
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