PT  - JOURNAL ARTICLE
AU  - Leroux
AU  - Roué
AU  - Gouyon
AU  - Biran
AU  - Zheng
AU  - Zhao
AU  - Jacqz-Aigrain
TI  - O-2 Population and developmental pharmacokinetic analysis to evaluate and optimise cefotaxime dosing regimen in neonates and young infants
AID  - 10.1136/archdischild-2017-esdppp.2
DP  - 2017 Oct 01
TA  - Archives of Disease in Childhood
PG  - A1--A1
VI  - 102
IP  - 10
4099  - http://adc.bmj.com/content/102/10/A1.2.short
4100  - http://adc.bmj.com/content/102/10/A1.2.full
SO  - Arch Dis Child2017 Oct 01; 102
AB  - Background Cefotaxime is one of the most frequently prescribed antibiotics for the treatment of Gram-negative bacterial sepsis in neonates. However, the dosing regi-mens routinely used in clinical practice vary considerably. The objective of the present study was to conduct a population pharmacokinetic study of cefotaxime in neonates and young infants in order to evaluate and optimise the dosing regimen.Methods An opportunistic sampling strategy com-bined with population pharmacokinetic analysis using NONMEM software was performed. Cefotaxime concentrations were measured by high-performance liquid chromatography tandem mass spectrometry. Developmental pharmacokinetics-pharmacodynamics, the microbiological pathogens, and safety aspects were taken into account to optimise the dose.Results The pharmacokinetic data from 100 neonates (gestational age [GA] range, 23 to 42 weeks) were modeled with an allometric two compartment model with first-order elimination. The median values for clearance and volume of distribution at steady state were 0.12 litre/h/kg of body weight and 0.64 litre/kg, respectively. The covariate analysis showed that current weight, GA, and postnatal age [PNA] had significant impacts on ce-fotaxime pharmacokinetics. Monte Carlo simulations demonstrated that the current dose recommendations underdosed the older newborns. A model-based dosing regimen of 50 mg/kg twice a day to four times a day, according to GA and PNA, was established. The associated risk of overdose for the proposed dosing regimen was 0.01%.Conclusion We determined the population pharma cokinetics of cefotaxime and established a model based dosing regimen to optimise treatment for neonates and young infants.