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Expert Opin Drug Metab Toxicol. 2016;12(4):367-75. doi: 10.1517/17425255.2016.1147559. Epub 2016 Feb 15.

Quantitative clinical pharmacology practice for optimal use of antibiotics during the neonatal period.

Author information

a Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty , University of Belgrade , Belgrade , Serbia.
b Division of Paediatric Pharmacology and Pharmacometrics , University of Basel Children's Hospital , Basel , Switzerland.
c Department of Development and Regeneration , KU Leuven , Leuven , Belgium.
d Intensive Care and Department of Pediatric Surgery , Erasmus MC Sophia Children's Hospital , Rotterdam , the Netherlands.
e Division of Pediatric Clinical Pharmacology , Children's National Medical Center , Washington , DC , USA.



For safe and effective neonatal antibiotic therapy, knowledge of the pharmacokinetic parameters of antibacterial agents in neonates is a prerequisite. Fast maturational changes during the neonatal period influence pharmacokinetic and pharmacodynamic parameters and their variability. Consequently, the need for applying quantitative clinical pharmacology and determining optimal drug dosing regimens in neonates has become increasingly recognized.


Modern quantitative approaches, such as pharmacometrics, are increasingly utilized to characterize, understand and predict the pharmacokinetics of a drug and its effect, and to quantify the variability in the neonatal population. Individual factors, called covariates in modeling, are integrated in such approaches to explain inter-individual pharmacokinetic variability. Pharmacometrics has been shown to be a relevant tool to evaluate, optimize and individualize drug dosing regimens.


Challenges for optimal use of antibiotics in neonates can largely be overcome with quantitative clinical pharmacology practice. Clinicians should be aware that there is a next step to support the clinical decision-making based on clinical characteristics and therapeutic drug monitoring, through Bayesian-based modeling and simulation methods. Pharmacometric modeling and simulation approaches permit us to characterize population average, inter-subject and intra-subject variability of pharmacokinetic parameters such as clearance and volume of distribution, and to identify and quantify key factors that influence the pharmacokinetic behavior of antibiotics during the neonatal period.


Antibiotics; clinical pharmacology; modeling and simulation; neonate; pharmacometrics; therapeutic drug monitoring

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