TY  - JOUR
AU  - Kerec Kos, Mojca
AU  - Miksić, Mirjana
AU  - Jovanović, Marija
AU  - Roškar, Robert
AU  - Grosek, Štefan
AU  - Grabnar, Iztok
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3517
AB  - 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.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis
VL  - 141
DO  - 10.1016/j.ejps.2019.105095
ER  - 

@article{
author = "Kerec Kos, Mojca and Miksić, Mirjana and Jovanović, Marija and Roškar, Robert and Grosek, Štefan and Grabnar, Iztok",
year = "2020",
abstract = "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.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis",
volume = "141",
doi = "10.1016/j.ejps.2019.105095"
}

Kerec Kos, M., Miksić, M., Jovanović, M., Roškar, R., Grosek, Š.,& Grabnar, I.. (2020). Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis. in European Journal of Pharmaceutical Sciences
Elsevier., 141.
https://doi.org/10.1016/j.ejps.2019.105095

Kerec Kos M, Miksić M, Jovanović M, Roškar R, Grosek Š, Grabnar I. Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis. in European Journal of Pharmaceutical Sciences. 2020;141.
doi:10.1016/j.ejps.2019.105095 .

Kerec Kos, Mojca, Miksić, Mirjana, Jovanović, Marija, Roškar, Robert, Grosek, Štefan, Grabnar, Iztok, "Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis" in European Journal of Pharmaceutical Sciences, 141 (2020),
https://doi.org/10.1016/j.ejps.2019.105095 . .