{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T12:18:32Z","timestamp":1793449112724,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Science and Technological Development, Republic of Serbia","award":["451-03-47\/2023-01\/200161"],"award-info":[{"award-number":["451-03-47\/2023-01\/200161"]}]},{"name":"Ministry of Education, Science and Technological Development, Republic of Serbia","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"Zoll foundation","award":["451-03-47\/2023-01\/200161"],"award-info":[{"award-number":["451-03-47\/2023-01\/200161"]}]},{"name":"Zoll foundation","award":["2022"],"award-info":[{"award-number":["2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients\u2019 individual PK parameters and corresponding concentration\u2013time profiles using the PopPK model, following the administration of 600 mg\/8 h (a higher-than-standard dosing) and 600 mg\/12 h (standard). The probabilities of pharmacokinetic\/pharmacodynamic (PK\/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg\/8 h was predicted to achieve greater than or equal to 85%Tf&gt;MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg\/L. In addition, for the same MIC, fAUC24\/MIC \u2265 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK\/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.<\/jats:p>","DOI":"10.3390\/pharmaceutics16020253","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T03:53:46Z","timestamp":1707450826000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Population Pharmacokinetic Model of Linezolid and Probability of Target Attainment in Patients with COVID-19-Associated Acute Respiratory Distress Syndrome on Veno-Venous Extracorporeal Membrane Oxygenation\u2014A Step toward Correct Dosing"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6087-5785","authenticated-orcid":false,"given":"Dragana","family":"Milakovi\u0107","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine and Thyroid Gland Diseases, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3924-7962","authenticated-orcid":false,"given":"Tijana","family":"Kova\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Pharmacy Department, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"},{"name":"Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-5351","authenticated-orcid":false,"given":"Pedja","family":"Kova\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina"},{"name":"Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-9583","authenticated-orcid":false,"given":"Vedrana","family":"Bari\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Pharmacy Department, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Avram","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Diagnostic, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2406-0588","authenticated-orcid":false,"given":"Sa\u0161a","family":"Dragi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina"},{"name":"Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Zlojutro","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina"},{"name":"Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danica","family":"Mom\u010di\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina"},{"name":"Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branislava","family":"Miljkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade-Faculty of Pharmacy, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-5785","authenticated-orcid":false,"given":"Katarina","family":"Vu\u010di\u0107evi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade-Faculty of Pharmacy, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22799036231151762","DOI":"10.1177\/22799036231151762","article-title":"Boosting ICU capacity during the COVID-19 pandemic in the western Balkan region, The Republic of Srpska experience","volume":"12","author":"Kovacevic","year":"2023","journal-title":"J. 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