Kim Annink

205 Pharmacokinetics of allopurinol in the ALBINO trial Figure 6: Goodness of fit plots for oxypurinol DISCUSSION This study showed that the target concentrations for allopurinol and oxypurinol in the ALBINO trial were met with the current dosing regimen for infants with HIE treated with and without therapeutic hypothermia. Therefore, changes in the dosing regimen in the ALBINO trial were deemed not necessary. This is the first study assessing the PK of allopurinol in infants with HIE treated with therapeutic hypothermia, as well as the first model including both allopurinol and oxypurinol PK in neonates (26). Nine out of 15 patients had allopurinol concentrations above the upper limit for therapeutic concentrations in adults for gout. High concentrations of allopurinol are important for its ability to directly scavenge free radicals and chelate non-protein-bound iron (8,9). Van Kesteren et al. previously described the PK of allopurinol in non-cooled infants with severe HIE (27). Data were used from two postnatal studies in which two doses of 20 mg/kg (first dose within 4 hours after birth and second dose 12 hours later) were administered (18,19,27). Like in the ALBINO PK study, a one compartment model best described their allopurinol data (27). The clearance of allopurinol in the cohort of van Kesteren et al. was 0.078 L/h/kg and in our study the clearance was 0.34 L/h (=0.097L/h/kg) for allopurinol. 9