title: The pharmacokinetics of dexmedetomidine during long-term infusion in critically ill pediatric patients. A Bayesian approach with informative priors.
abstract: The purpose of this study was to assess the pharmacokinetics of dexmedetomidine in the ICU settings during the prolonged infusion and to compare it with the existing literature data using the Bayesian population modeling with literature-based informative priors. Thirty-eight patients were included in the analysis with concentration measurements obtained at two occasions: first from 0 to 24 h after infusion initiation and second from 0 to 8 h after infusion end. Data analysis was conducted using WinBUGS software. The prior information on dexmedetomidine pharmacokinetics was elicited from the literature study pooling results from a relatively large group of 95 children. A two compartment PK model, with allometrically scaled parameters, maturation of clearance and t-student residual distribution on a log-scale was used to describe the data. The incorporation of time-dependent (different between two occasions) PK parameters improved the model. It was observed that volume of distribution is 1.5-fold higher during the second occasion. There was also an evidence of increased (1.3-fold) clearance for the second occasion with posterior probability equal to 62 %. This work demonstrated the usefulness of Bayesian modeling with informative priors in analyzing pharmacokinetic data and comparing it with existing literature knowledge.
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gdansk, Poland. wiczling@gumed.edu.pl.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Szpitalna Street 27/33, 60572, Poznan, Poland. asniatko@ump.edu.pl.
authors.forename: Alicja
authors.initials: A
authors.lastname: Bartkowska-Śniatkowska
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Oliwia
authors.initials: O
authors.lastname: Szerkus
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Siluk
authors.affiliation: Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Szpitalna Street 27/33, 60572, Poznan, Poland.
authors.forename: Jowita
authors.initials: J
authors.lastname: Rosada-Kurasińska
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Warzybok
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Borsuk
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Kaliszan
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bienert
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D008954:Models, Biological; D012984:Software; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine
keywords: Dexmedetomidine; Informative priors; Population pharmacokinetics; WinBUGS