In newborn infants, allopurinol is being tested as a free radical scavenger to 
prevent brain damage caused by reperfusion and oxygenation after perinatal 
hypoxia and ischemia (birth asphyxia). To develop rational dosing schemes for 
future studies, knowledge of the pharmacokinetics in this patient group is 
essential. In the present study, a population pharmacokinetic model was designed 
and validated for allopurinol in this specific patient group. One-compartment 
and 2-compartment models were fitted to plasma concentration time data of 24 
newborns entered in 2 clinical trials using nonlinear mixed effects modeling. A 
bootstrap procedure was performed to check the robustness of the model. The data 
were best described using a 1-compartment model with linear elimination. 
Estimated pharmacokinetic parameters were volume of the central compartment (V, 
0.79 L/kg) and total body clearance (CL, 0.078 L/h/kg), with 42% and 60% 
interindividual variability, respectively. The median values for these 
parameters of 1000 bootstrap replicates were very similar (95% confidence 
intervals were 0.67 to 0.96 and 0.054 to 0.10 for V and CL, respectively), 
indicating the robustness of the model. A population pharmacokinetic model has 
been designed and validated which adequately describes the data of 2 clinical 
studies in critically ill newborn infants. The model will be used to design 
dosing strategies for future evaluation of the benefits of allopurinol in these 
patients.