title: Pharmacokinetics of sufentanil during long-term infusion in critically ill pediatric patients.
abstract: The aim of this study was to develop a population pharmacokinetic model of sufentanil and to assess the influence of covariates in critically ill children admitted to a pediatric intensive care unit. After institutional approval, 41 children were enrolled in the study. Blood samples for pharmacokinetic (PK) assessment were collected from routinely placed arterial catheters during and after discontinuation of infusion. Population nonlinear mixed-effects modeling was performed using NONMEM. A 2-compartment model described sufentanil PK sufficiently. Typical values of the central and peripheral volume of distribution and the metabolic and intercompartmental clearance for a theoretical patient weighing 70 kg were VC = 7.90 l, VT  = 481 L, Cl =  5.3 L/h, and Q = 38.3 L/h, respectively. High interindividual variability of all PK parameters was noted. Allometric/isometric principles to scale sufentanil PK revealed that to achieve the same steady-state sufentanil concentrations in plasma for pediatric patients of different body weights, the infusion rate should follow the formula (infusion rate for a 70-kg adult patient, μg/h) × (body weight/70 kg)(0.75). Severity of illness described by PRISM score, the monitored physiological and laboratory parameters, and coadministered drugs such as vasopressors were not found to be significant covariates.
authors.affiliation: Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Bartkowska-Śniatkowska
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bienert
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Jowita
authors.initials: J
authors.lastname: Rosada-Kurasińska
authors.affiliation: Department of Anesthesiology and Intensive Care, Pediatric Intensive Care Unit, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Zielińska
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: Intensive Care and Department of Pediatric Surgery, Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
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
mesh_terms: D000293:Adolescent; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D005260:Female; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008297:Male; D008954:Models, Biological; D017409:Sufentanil / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; D017409:Sufentanil
keywords: critical ill children; population PK; sedation; sufentanil