Avtor/Urednik		Kerec Kos, Mojca; Miksić, Mirjana; Jovanović, Marija; Roškar, Robert; Grosek, Štefan; Grabnar, Iztok
Naslov		Maturation of midazolam clearance in critically ill children with severe bronchiolitis
Tip		članek
Vol. in št.		, št. Vol. 141
Leto izdaje		2020
Obseg		str. 1-7
ISSN		1879-0720 - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Jezik		eng
Abstrakt		Purpose The aim of the present study was to develop a population pharmacokinetic model of midazolam, and to evaluate the influence of maturation process and other variability factors in critically ill children with severe acute bronchiolitis, who received a long-term intravenous infusion of midazolam. Methods In the study were included 49 critically ill children of both genders (from 0 to 130 weeks of age) with severe acute bronchiolitis hospitalised in intensive care units. Nonlinear mixed effects modelling approach was applied for data analyses and simulations. Results The final model is a two-compartment model that includes the effects of body weight using allometric scaling with fixed exponents and maturation of clearance. For a typical subject, scaled to the adult body weight of 70%kg, population pharmacokinetic values were estimated at 8.52%L/h for clearance (when maturation function was 1), 25.5%L/h for intercompartmental clearance, and 5.71%L and 39.8%L for the volume of the central and peripheral compartment, respectively. Based on the final model, maturation reaches 50% of the adult clearance in 45.9 weeks of postmenstrual age. The influence of gender, ABCB1 genotype and biochemical parameters on midazolam clearance was not detected. Results of simulations indicate the need for reduced dosing in certain groups of patients in order to maintain plasma concentrations of midazolam within recommended values. Conclusions The developed population pharmacokinetic model can contribute to the dosing optimisation of midazolam, especially in critically ill children as it includes the influence of size and maturation of clearance, which are important parameters for achieving the desired plasma concentrations of midazolam.
Deskriptorji		Midazolam Midazolam Bronchiolitis Bronhiolitis Pharmacokinetics Farmakokinetika Critical illness Kritična bolezen Child Otrok