{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:43:50Z","timestamp":1788234230961,"version":"build-2803163510"},"reference-count":23,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Cefiderocol is a siderophore cephalosporin antibiotic active against Gram-negative bacteria, including extended-spectrum beta-lactamase and carbapenemase-producing strains. The pharmacokinetics of cefiderocol has been studied in healthy subjects and particularly in phase II and III studies. This retrospective study investigated intravenous cefiderocol population pharmacokinetics in adult patients treated by cefiderocol. Methods: We studied 55 consecutive patients hospitalized in an intensive care unit. Cefiderocol plasma samples were obtained on different occasions during treatment. Plasma concentration was assayed using mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2020R1. Results: A total of 205 plasma samples were obtained from 55 patients. Eighty percent of patients received cefiderocol for ventilator-associated pneumonia due to carbapenem-resistant Pseudomonas aeruginosa infection. Cefiderocol concentration time-courses were best fit to a two-compartment open model with first-order elimination. Elimination clearance was positively related to renal function (estimated by the CKD formula). Adding albumin plasma binding in the model significantly improved the model assuming a ~40% unbound drug fraction given a ~40 g\/L albuminemia. The final model included CKD plus cefiderocol plasma binding effects. Fat-free mass was better than total body weight to influence, via the allometric rule, clearance and volume terms, but this effect was negligible. The final clearance based on free circulating drug (CLU) for a typical patient, CKD = 90, was 7.38 L\/h [relative standard error, RSE, 22%] with a between-subject variability of 0.47 [RSE 10%] (exponential distribution). Conclusion: This study showed that albumin binding and CKD effects were significant predictors of unbound and total plasma cefiderocol concentrations. Our results indicate that individual adjustment of cefiderocol can be used to reach high minimum inhibitory concentrations based on an estimation of unbound drug concentration and optimize therapeutic efficacy.<\/jats:p>","DOI":"10.3390\/pharmaceutics14122786","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T02:22:41Z","timestamp":1670984561000},"page":"2786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Total and Unbound Pharmacokinetics of Cefiderocol in Critically Ill Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"No\u00ebl","family":"Zahr","sequence":"first","affiliation":[{"name":"Pharmacokinetics and Therapeutic Drug Monitoring Unit, Department of Pharmacology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Inserm, CIC-1901, UMR-S 1166, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saik","family":"Urien","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche Clinique, H\u00f4pital Necker-Enfants Malades, AP-HP, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Llopis","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Therapeutic Drug Monitoring Unit, Department of Pharmacology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Inserm, CIC-1901, UMR-S 1166, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3864-6224","authenticated-orcid":false,"given":"Ga\u00eblle","family":"No\u00e9","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Therapeutic Drug Monitoring Unit, Department of Pharmacology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Inserm, CIC-1901, UMR-S 1166, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Tissot","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Therapeutic Drug Monitoring Unit, Department of Pharmacology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Inserm, CIC-1901, UMR-S 1166, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6797-0237","authenticated-orcid":false,"given":"Kevin","family":"Bihan","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Therapeutic Drug Monitoring Unit, Department of Pharmacology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Inserm, CIC-1901, UMR-S 1166, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Junot","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Marin","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Therapeutic Drug Monitoring Unit, Department of Pharmacology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Inserm, CIC-1901, UMR-S 1166, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bochra","family":"Mansour","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Therapeutic Drug Monitoring Unit, Department of Pharmacology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Inserm, CIC-1901, UMR-S 1166, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles-Edouard","family":"Luyt","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Intensive R\u00e9animation, Institut de Cardiologie, AP-HP Sorbonne-Universit\u00e9, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5145-4174","authenticated-orcid":false,"given":"Alexandre","family":"Bleibtreu","sequence":"additional","affiliation":[{"name":"Service de Maladies Infectieuses et Tropicales, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0406-5189","authenticated-orcid":false,"given":"Christian","family":"Funck-Brentano","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Therapeutic Drug Monitoring Unit, Department of Pharmacology, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Inserm, CIC-1901, UMR-S 1166, AP-HP Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1093\/jac\/dkab015","article-title":"Cefiderocol: A novel siderophore cephalosporin for multidrug-resistant Gram-negative bacterial infections","volume":"76","author":"Parsels","year":"2021","journal-title":"J. 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