{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:12:35Z","timestamp":1793419955414,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Multidrug-resistant Acinetobacter baumannii (MDR-A. baumannii) has become an emerging pathogen, causing ventilator-associated pneumonia (VAP), with limited treatment options available. MIN has re-emerged as a potential treatment option for MDR pathogens. However, evidence regarding MIN pharmacokinetic properties in critically ill patients is scarce and primarily limited to IV administration. To address the knowledge gap in regions where IV MIN is unavailable, a prospective, open-label study was conducted to describe the pharmacokinetic properties of orally administered MIN.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The study included 24 critically ill patients with MDR-A. baumannii VAP. A population PK (popPK) model was developed and the PTA for different MICs was assessed by Monte Carlo simulations. A one-compartment model with first-order absorption and linear elimination best described the data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The values of the estimated population parameters were found equal to 183.3\u2005L, 6.55\u2005L\/h and 1.66\u2005h\u207b\u00b9, for the apparent volume of distribution (V\/F), the apparent clearance (CL\/F) and the absorption rate constant (ka), respectively (F representing oral bioavailability). PTA analysis showed that for a daily dose of 400\u2005mg, adequate exposure [free AUC\/MIC (fAUC\/MIC\u200a&amp;gt;\u200a25)] was achieved only for MICs\u200a\u2264\u200a0.25\u2005mg\/L, while for the ratio of fAUC\/MIC\u200a=\u200a13.75, high PTA values are calculated up to MIC\u200a=\u200a0.5\u2005mg\/L.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study provides a popPK model for oral MIN in critically ill adults. The developed popPK model contributes to a better understanding of MIN\u2019s PK and can inform dosing strategies and future studies on MIN use in critical care settings.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaf090","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T08:33:11Z","timestamp":1743237191000},"page":"1420-1426","source":"Crossref","is-referenced-by-count":3,"title":["Population pharmacokinetic model of oral minocycline in critically ill adult patients with ventilator-associated pneumonia"],"prefix":"10.1093","volume":"80","author":[{"given":"Zoe","family":"Athanassa","sequence":"first","affiliation":[{"name":"Intensive Care Unit, Sismanogleio General Hospital , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraskevi","family":"Papakyriakopoulou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National and Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Marquez Megias","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Miguel Hern\u00e1ndez University , San Juan de Alicante ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmina-Marina","family":"Saitani","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National and Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Manioudaki","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Sismanogleio General Hospital , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Dimoula","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Sismanogleio General Hospital , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Petsa","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Sismanogleio General Hospital , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Valsami","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National and Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Sakagianni","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Sismanogleio General Hospital , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Koumaki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, National and Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-4003","authenticated-orcid":false,"given":"Aristides","family":"Dokoumetzidis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National and Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanassios","family":"Tsakris","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, National and Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"2025050205521715700_dkaf090-B1","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1007\/s00134-020-05980-0","article-title":"Ventilator-associated pneumonia in adults: a narrative review","volume":"46","author":"Papazian","year":"2020","journal-title":"Intensive Care Med"},{"key":"2025050205521715700_dkaf090-B2","doi-asserted-by":"publisher","first-page":"103227","DOI":"10.1016\/j.iccn.2022.103227","article-title":"Healthcare-associated infections in adult intensive care unit patients: changes in epidemiology, diagnosis, prevention and contributions of new technologies","volume":"70","author":"Blot","year":"2022","journal-title":"Intensive Crit Care Nurs"},{"key":"2025050205521715700_dkaf090-B3","volume-title":"Carbapenem-resistant Acinetobacter: An Urgent Public Health Threat","author":"Centers for Disease Control and Prevention","year":"2021"},{"key":"2025050205521715700_dkaf090-B4","doi-asserted-by":"publisher","first-page":"261","DOI":"10.3390\/antibiotics13030261","article-title":"Current therapeutic approaches for multidrug-resistant and extensively drug-resistant Acinetobacter baumannii infections","volume":"13","author":"Rafailidis","year":"2024","journal-title":"Antibiotics"},{"key":"2025050205521715700_dkaf090-B5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3390\/microorganisms7060159","article-title":"The role of minocycline in the treatment of nosocomial infections caused by multidrug, extensively drug and pandrug resistant Acinetobacter baumannii: a systematic review of clinical evidence","volume":"7","author":"Fragkou","year":"2019","journal-title":"Microorganisms"},{"key":"2025050205521715700_dkaf090-B6","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1093\/cid\/ciz173","article-title":"A primer on AmpC \u03b2-lactamases: necessary knowledge for an increasingly multidrug-resistant world","volume":"69","author":"Tamma","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2025050205521715700_dkaf090-B7","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s40121-017-0153-2","article-title":"Minocycline for the treatment of multidrug and extensively drug-resistant A. baumannii: a review","volume":"6","author":"Lashinsky","year":"2017","journal-title":"Infect Dis Ther"},{"key":"2025050205521715700_dkaf090-B8","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1093\/jac\/dkl224","article-title":"Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines","volume":"58","author":"Agwuh","year":"2006","journal-title":"J Antimicrob Chemother"},{"key":"2025050205521715700_dkaf090-B9","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1111\/bph.12139","article-title":"Minocycline: far beyond an antibiotic","volume":"169","author":"Garrido-Mesa","year":"2013","journal-title":"Br J Pharmacol"},{"key":"2025050205521715700_dkaf090-B10","volume-title":"Minocin (minocycline) for Injection\u2014Full Prescribing Information (Label Update 2024)","author":"U.S. Food and Drug Administration (FDA)","year":"2024"},{"issue":"Suppl 6","key":"2025050205521715700_dkaf090-B11","doi-asserted-by":"publisher","first-page":"S374","DOI":"10.1093\/cid\/ciu613","article-title":"A review of intravenous minocycline for treatment of multidrug-resistant Acinetobacter infections","volume":"59","author":"Ritchie","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2025050205521715700_dkaf090-B12","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1128\/MMBR.65.2.232-260.2001","article-title":"Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance","volume":"65","author":"Chopra","year":"2001","journal-title":"Microbiol Mol Biol Rev"},{"key":"2025050205521715700_dkaf090-B13","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1002\/cpt1973145852","article-title":"Pharmacokinetic studies on minocycline in man","volume":"14","author":"Macdonald","year":"1973","journal-title":"Clin Pharmacol Ther"},{"key":"2025050205521715700_dkaf090-B14","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1111\/j.1440-1681.1974.tb00552.x","article-title":"Minocycline excretion and distribution in relation to renal function in man","volume":"1","author":"Carney","year":"1974","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2025050205521715700_dkaf090-B15","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1128\/aac.8.5.532","article-title":"Pharmacokinetics of minocycline in renal failure","volume":"8","author":"Welling","year":"1975","journal-title":"Antimicrob Agents Chemother"},{"key":"2025050205521715700_dkaf090-B16","doi-asserted-by":"publisher","first-page":"e01809-20","DOI":"10.1128\/AAC.01809-20","article-title":"Pharmacokinetic and pharmacodynamic profiling of minocycline for injection following a single infusion in critically ill adults in a phase IV open-label multicenter study (ACUMIN)","volume":"65","author":"Lodise","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2025050205521715700_dkaf090-B17","first-page":"46","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing","author":"CLSI","year":"2020","edition":"30th edn"},{"key":"2025050205521715700_dkaf090-B18","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1093\/jac\/dky448","article-title":"Minocycline susceptibility breakpoints for Acinetobacter baumannii: do we need to re-evaluate them?","volume":"74","author":"Tsakris","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2025050205521715700_dkaf090-B19","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s40262-023-01213-x","article-title":"Pharmacokinetic alterations associated with critical illness","volume":"62","author":"Morales Castro","year":"2023","journal-title":"Clin Pharmacokinet"},{"key":"2025050205521715700_dkaf090-B20","doi-asserted-by":"publisher","first-page":"104463","DOI":"10.1016\/j.jddst.2023.104463","article-title":"Nose-to-brain delivery of donepezil hydrochloride following administration of an HPMC-Me-\u03b2-CD-PEG400 nasal film in mice","volume":"84","author":"Papakyriakopoulou","year":"2023","journal-title":"J Drug Deliv Sci Technol"},{"key":"2025050205521715700_dkaf090-B21","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3947\/ic.2021.0007","article-title":"Colistin plus sulbactam or fosfomycin against carbapenem-resistant Acinetobacter baumannii: improved efficacy or decreased risk of nephrotoxicity?","volume":"53","author":"Saelim","year":"2021","journal-title":"Infect Chemother"},{"key":"2025050205521715700_dkaf090-B22","doi-asserted-by":"publisher","first-page":"e01671-18","DOI":"10.1128\/AAC.01671-18","article-title":"Pharmacodynamics of minocycline against Acinetobacter baumannii in a rat pneumonia model","volume":"63","author":"Tarazi","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2025050205521715700_dkaf090-B23","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1001\/jama.286.14.1754","article-title":"Serial evaluation of the SOFA score to predict outcome in critically ill patients","volume":"286","author":"Ferreira","year":"2001","journal-title":"JAMA"},{"key":"2025050205521715700_dkaf090-B24","doi-asserted-by":"publisher","first-page":"355","DOI":"10.2165\/00003088-198815060-00001","article-title":"Clinical pharmacokinetics of doxycycline and minocycline","volume":"15","author":"Saivin","year":"1988","journal-title":"Clin Pharmacokinet"},{"key":"2025050205521715700_dkaf090-B25","doi-asserted-by":"publisher","first-page":"3303","DOI":"10.1093\/jac\/dkae363","article-title":"Population pharmacokinetics\/pharmacodynamics of minocycline plus rifampicin in patients with complicated skin and skin structure infections caused by MRSA","volume":"79","author":"Pardos","year":"2024","journal-title":"J Antimicrob Chemother"},{"key":"2025050205521715700_dkaf090-B26","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1093\/jac\/23.1.123","article-title":"Doxycycline and minocycline in the treatment of respiratory infections: a double-blind comparative clinical, microbiological and pharmacokinetic study","volume":"23","author":"Maesen","year":"1989","journal-title":"J Antimicrob Chemother"},{"key":"2025050205521715700_dkaf090-B27","first-page":"1022","article-title":"Pharmacokinetic comparison of once-daily topical minocycline foam 4% vs oral minocycline for moderate-to-severe acne","volume":"16","author":"Jones","year":"2017","journal-title":"J Drugs Dermatol"},{"key":"2025050205521715700_dkaf090-B28","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1177\/1098612X15579114","article-title":"Pharmacokinetics of minocycline in domestic cats","volume":"18","author":"Tynan","year":"2016","journal-title":"J Feline Med Surg"},{"key":"2025050205521715700_dkaf090-B29","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/vde.12246","article-title":"Effect of feeding on the pharmacokinetics of oral minocycline in healthy research dogs","volume":"26","author":"Hnot","year":"2015","journal-title":"Vet Dermatol"},{"key":"2025050205521715700_dkaf090-B30","first-page":"45","article-title":"Pharmacocinetique de la minocycline chez l'homme","volume":"90","author":"Fourtillan","year":"1983","journal-title":"Gaz Med Fr"},{"key":"2025050205521715700_dkaf090-B31","doi-asserted-by":"publisher","first-page":"e02371-16","DOI":"10.1128\/AAC.02371-16","article-title":"Pharmacokinetics and pharmacodynamics of minocycline against Acinetobacter baumannii in a neutropenic murine pneumonia model","volume":"61","author":"Zhou","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2025050205521715700_dkaf090-B32","doi-asserted-by":"publisher","first-page":"e5351","DOI":"10.7759\/cureus.5351","article-title":"Reconsidering the use of minocycline in the preliminary treatment regime of rheumatoid arthritis","volume":"11","author":"Heydari-Kamjani","year":"2019","journal-title":"Cureus"},{"key":"2025050205521715700_dkaf090-B33","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.2174\/1567205013666160819124206","article-title":"The anti-inflammatory role of minocycline in Alzheimer\u00b4s disease","volume":"13","author":"Budni","year":"2016","journal-title":"Curr Alzheimer Res"},{"key":"2025050205521715700_dkaf090-B34","doi-asserted-by":"publisher","first-page":"212553","DOI":"10.7573\/dic.212553","article-title":"The therapeutic role of minocycline in Parkinson's disease","volume":"8","author":"Cankaya","year":"2019","journal-title":"Drugs Context"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/5\/1420\/62711083\/dkaf090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/5\/1420\/62711083\/dkaf090.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T09:52:24Z","timestamp":1746179544000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/80\/5\/1420\/8093441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,26]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3,26]]},"published-print":{"date-parts":[[2025,5,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkaf090","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,5]]},"published":{"date-parts":[[2025,3,26]]}}}