The pharmacokinetics of propofol in ICU patients undergoing long-term sedation

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‐eff...

Full description

Saved in:
Bibliographic Details
Published in:Biopharmaceutics & drug disposition 2016-11, Vol.37 (8), p.456-466
Main Authors: Smuszkiewicz, Piotr, Wiczling, Paweł, Przybyłowski, Krzysztof, Borsuk, Agnieszka, Trojanowska, Iwona, Paterska, Marta, Matysiak, Jan, Kokot, Zenon, Grześkowiak, Edmund, Bienert, Agnieszka
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Drug Administration Schedule
Female
Humans
Hypnotics and Sedatives - administration & dosage
Hypnotics and Sedatives - pharmacokinetics
Infusions, Intravenous
Intensive Care Units - trends
long-term sedation
Male
mechanical ventilation
Middle Aged
pharmacokinetics
propofol
Propofol - administration & dosage
Propofol - pharmacokinetics
Time Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0142-2782
1099-081X
DOI:10.1002/bdd.2028