TY  - CONF
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
AU  - Kovačević, Milena
AU  - Slavković, Bojana
AU  - Rakonjac, Zorica
AU  - Prostran, Milica
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4742
AB  - Objectives: The aim of this study was to explore the influence of demographic and clinical
covariates, and hence to develop population pharmacokinetic (PK) model of amikacin in
neonates with suspected or proven sepsis.
Methods: In total 39 neonates born at term (≥37 weeks gestational age, GA) were included in
the study. Amikacin was administered over 1 h infusion, using multiple or once-daily dosing
schedule, with daily dose of 15 mg/kg (if postnatal age, AGE ≤7 days) or 20 mg/kg (if AGE >7
days). Two samples were taken per patient, corresponding to the peak and trough serum
concentration. The population PK analysis was performed using NONMEM® software (ver.6.2).
Internal validation was performed.
Results: Linear one-compartment model with a proportional interindividual error and combined
residual error model were used to describe PK of amikacin. The final population model for
clearance is: CL(l/h)=0.12·(TM/4)·0.75·1.31·GA·1.33·AGE, where GA=0 for 37-38 gestational
weeks, GA= 1 for 39-42 gestational weeks; AGE=0 for postnatal age ≤7 days, AGE=1 for
postnatal age >7 days; whereas volume of distribution was weight normalized, and
interindividual error was not modeled. The results show that clearance is increased in average by
31 % in neonates of 39-42 gestational weeks compared to neonates of 37-38 gestational weeks,
and it was increased in average by 33 % with postnatal age >7 days. The estimate of clearance
for a typical patient was 0.12 (0.106 - 0.134) l/h, while interindividual variability of clearance in
the studied population was 24.72 (11.79 – 32.91) %, the residual variability estimated the
proportional error at 54.41 % and additive error 61.07 μg/mL.
Conclusions: The results suggest that amikacin elimination increases with gestational and
postnatal age presumably owing to the process of maturation that is extensively carried out in the
first weeks of life. Final population pharmacokinetic model for amikacin can be used to predict
the individual concentration of amikacin in neonates, and individualization of therapy.
PB  - Population Approach Group Europe (PAGE)
C3  - 20th Population Approach Group Europe (PAGE 20), 7-10 June, 2011. Athens, Greece
T1  - Population Pharmacokinetic Modelling of Amikacin in Neonates
SP  - 371
EP  - 371
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4742
ER  - 

@conference{
author = "Vučićević, Katarina and Miljković, Branislava and Kovačević, Milena and Slavković, Bojana and Rakonjac, Zorica and Prostran, Milica",
year = "2011",
abstract = "Objectives: The aim of this study was to explore the influence of demographic and clinical
covariates, and hence to develop population pharmacokinetic (PK) model of amikacin in
neonates with suspected or proven sepsis.
Methods: In total 39 neonates born at term (≥37 weeks gestational age, GA) were included in
the study. Amikacin was administered over 1 h infusion, using multiple or once-daily dosing
schedule, with daily dose of 15 mg/kg (if postnatal age, AGE ≤7 days) or 20 mg/kg (if AGE >7
days). Two samples were taken per patient, corresponding to the peak and trough serum
concentration. The population PK analysis was performed using NONMEM® software (ver.6.2).
Internal validation was performed.
Results: Linear one-compartment model with a proportional interindividual error and combined
residual error model were used to describe PK of amikacin. The final population model for
clearance is: CL(l/h)=0.12·(TM/4)·0.75·1.31·GA·1.33·AGE, where GA=0 for 37-38 gestational
weeks, GA= 1 for 39-42 gestational weeks; AGE=0 for postnatal age ≤7 days, AGE=1 for
postnatal age >7 days; whereas volume of distribution was weight normalized, and
interindividual error was not modeled. The results show that clearance is increased in average by
31 % in neonates of 39-42 gestational weeks compared to neonates of 37-38 gestational weeks,
and it was increased in average by 33 % with postnatal age >7 days. The estimate of clearance
for a typical patient was 0.12 (0.106 - 0.134) l/h, while interindividual variability of clearance in
the studied population was 24.72 (11.79 – 32.91) %, the residual variability estimated the
proportional error at 54.41 % and additive error 61.07 μg/mL.
Conclusions: The results suggest that amikacin elimination increases with gestational and
postnatal age presumably owing to the process of maturation that is extensively carried out in the
first weeks of life. Final population pharmacokinetic model for amikacin can be used to predict
the individual concentration of amikacin in neonates, and individualization of therapy.",
publisher = "Population Approach Group Europe (PAGE)",
journal = "20th Population Approach Group Europe (PAGE 20), 7-10 June, 2011. Athens, Greece",
title = "Population Pharmacokinetic Modelling of Amikacin in Neonates",
pages = "371-371",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4742"
}

Vučićević, K., Miljković, B., Kovačević, M., Slavković, B., Rakonjac, Z.,& Prostran, M.. (2011). Population Pharmacokinetic Modelling of Amikacin in Neonates. in 20th Population Approach Group Europe (PAGE 20), 7-10 June, 2011. Athens, Greece
Population Approach Group Europe (PAGE)., 371-371.
https://hdl.handle.net/21.15107/rcub_farfar_4742

Vučićević K, Miljković B, Kovačević M, Slavković B, Rakonjac Z, Prostran M. Population Pharmacokinetic Modelling of Amikacin in Neonates. in 20th Population Approach Group Europe (PAGE 20), 7-10 June, 2011. Athens, Greece. 2011;:371-371.
https://hdl.handle.net/21.15107/rcub_farfar_4742 .

Vučićević, Katarina, Miljković, Branislava, Kovačević, Milena, Slavković, Bojana, Rakonjac, Zorica, Prostran, Milica, "Population Pharmacokinetic Modelling of Amikacin in Neonates" in 20th Population Approach Group Europe (PAGE 20), 7-10 June, 2011. Athens, Greece (2011):371-371,
https://hdl.handle.net/21.15107/rcub_farfar_4742 .