{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:57:16Z","timestamp":1792112236333,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dexmedetomidine is a hepatically eliminated drug with sedative, anxiolytic, sympatholytic, and analgesic properties that has been increasingly used for various indications in the form of a short or continuous intravenous infusion. This study aimed to propose a population pharmacokinetic (PK) model of dexmedetomidine in a heterogeneous group of intensive care unit patients, incorporating 29 covariates potentially linked with dexmedetomidine PK. Data were collected from 70 patients aged between 0.25 and 88 years and treated with dexmedetomidine infusion for various durations at 1 of 4 medical centers. Statistical analysis was performed using a nonlinear mixed\u2010effect model. Categorical and continuous covariates including demographic data, hemodynamic parameters, biochemical markers, and 11 single\u2010nucleotide polymorphisms were tested. A 2\u2010compartment model was used to describe dexmedetomidine PK. An allometric\/isometric scaling was used to account for body weight difference in PK parameters, and the Hill equation was used to describe the maturation of clearance. Typical values of the central and peripheral volume of distribution and the systemic and distribution clearance for a theoretical adult patient were central volume of distribution = 22.50 L, peripheral volume of distribution \u2009= 86.1 L, systemic clearance =\u2009 34.7 L\/h, and distribution clearance = 40.8 L\/h. The\n                    <jats:italic>CYP1A2<\/jats:italic>\n                    genetic polymorphism and noradrenaline administration were identified as significant covariates for clearance. A population PK model of dexmedetomidine was successfully developed. The proposed model is well calibrated to the observed data. The identified covariates account for &lt;5% of interindividual variability and consequently are of low clinical significance for the purpose of dose adjustment.\n                  <\/jats:p>","DOI":"10.1002\/jcph.1647","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T04:14:12Z","timestamp":1591330452000},"page":"1461-1473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Population Pharmacokinetic Model of Dexmedetomidine in a Heterogeneous Group of Patients"],"prefix":"10.1002","volume":"60","author":[{"given":"Justyna","family":"Ber","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Biopharmacy Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-3161","authenticated-orcid":false,"given":"Pawe\u0142","family":"Wiczling","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy and Pharmacodynamics Medical University of Gdansk  Gdansk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Ho\u0142ysz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Klupczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Bartkowska\u2010\u015aniatkowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Anesthesiology and Intensive Therapy Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Bieda","sequence":"additional","affiliation":[{"name":"Anaesthesiology and Intensive Care Department Greater Poland Cancer Centre  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Smuszkiewicz","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Intensive Therapy and Pain Treatment Heliodor Swiecicki Clinical Hospital Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Nowicka","sequence":"additional","affiliation":[{"name":"Anaesthetics and Critical Care Department University Hospital of Lord's Transfiguration Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"\u017bura\u0144ski","sequence":"additional","affiliation":[{"name":"Anaesthetics and Critical Care Department University Hospital of Lord's Transfiguration Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Sobczy\u0144ski","sequence":"additional","affiliation":[{"name":"Anaesthetics and Critical Care Department University Hospital of Lord's Transfiguration Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Matysiak","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund","family":"Grze\u015bkowiak","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Biopharmacy Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Bienert","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Biopharmacy Poznan University of Medical Sciences  Poznan Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"United States Food and Drug Administration (FDA).FDA Approved Drug Products \u2013 Precedex Label.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/1999\/21038lbl.pdf. 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