title: The pharmacokinetics of propofol in ICU patients undergoing long-term sedation.
abstract: The aim of this study was to characterize the pharmacokinetics (PK) of propofol in ICU patients undergoing long-term sedation and to assess the influence of routinely collected covariates on the PK parameters. Propofol concentration-time profiles were collected from 29 patients. Non-linear mixed-effects modelling in NONMEM 7.2 was used to analyse the observed data. The propofol pharmacokinetics was best described with a three-compartment disposition model. Non-parametric bootstrap and a visual predictive check were used to evaluate the adequacy of the developed model to describe the observations. The typical value of the propofol clearance (1.46 l/min) approximated the hepatic blood flow. The volume of distribution at steady state was high and was equal to 955.1 l, which is consistent with other studies involving propofol in ICU patients. There was no statistically significant covariate relationship between PK parameters and opioid type, SOFA score on the day of admission, APACHE II, predicted death rate, reason for ICU admission (sepsis, trauma or surgery), gender, body weight, age, infusion duration and C-reactive protein concentration. The population PK model was developed successfully to describe the time-course of propofol concentration in ICU patients undergoing prolonged sedation. Despite a very heterogeneous group of patients, consistent PK profiles were observed. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Anaesthesiology and Intensive Therapy, Karol Marcinkowski University of Medical Sciences, ul. Przybyszewskiego 49, 60-355, Poznań, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Smuszkiewicz
authors.affiliation: Department of Biopharmacy and Pharmacodynamics, Medical University of Gdansk, ul. Hallera 107, 80-416, Gdańsk, Poland. wiczling@gumed.edu.pl.
authors.forename: Paweł
authors.identifier: http://orcid.org/0000-0002-2878-3161
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, ul. Grunwaldzka 6, 60-780, Poznań, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Przybyłowski
authors.affiliation: Department of Biopharmacy and Pharmacodynamics, Medical University of Gdansk, ul. Hallera 107, 80-416, Gdańsk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Borsuk
authors.affiliation: Department of Anaesthesiology and Intensive Therapy, Karol Marcinkowski University of Medical Sciences, ul. Przybyszewskiego 49, 60-355, Poznań, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Trojanowska
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, ul. Grunwaldzka 6, 60-780, Poznań, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Paterska
authors.affiliation: Department of Inorganic and Analytical Chemistry, Karol Marcinkowski University of Medical Sciences, ul. Grunwaldzka 6, 60-780, Poznań, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Matysiak
authors.affiliation: Department of Inorganic and Analytical Chemistry, Karol Marcinkowski University of Medical Sciences, ul. Grunwaldzka 6, 60-780, Poznań, Poland.
authors.forename: Zenon
authors.identifier: http://orcid.org/0000-0003-4950-9759
authors.initials: Z
authors.lastname: Kokot
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, ul. Grunwaldzka 6, 60-780, Poznań, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Karol Marcinkowski University of Medical Sciences, ul. Grunwaldzka 6, 60-780, Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bienert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007362:Intensive Care Units / Q000639:trends; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D015742:Propofol
keywords: long-term sedation; mechanical ventilation; pharmacokinetics; propofol