Kim Annink

203 Pharmacokinetics of allopurinol in the ALBINO trial A one-compartment model for allopurinol and a subsequent one-compartment model for its metabolite oxypurinol were developed to describe the PK of allopurinol and oxypurinol. To reduce the complexity of model, interindividual variabilities of Vd were omitted. Population pharmacokinetic parameters estimated were normalized to a BW of 3.5 kg and are described in Table 3. Table 3: Population PK parameters (mean) for allopurinol and oxypurinol in infants treated with and without therapeutic hypothermia. Parameter Allopurinol Oxypurinol * Structural model Estimate SIR 95%CI Estimate SIR 95%CI Clearance (L/h) 0.34 0.27-0.41 0.31 0.21-0.45 Vd (L) 3.79 3.40-4.26 5.54 4.79-6.42 Interindividual variability Clearance (%) 34.6 76.2 Residual variability Proportional (%) 15 24 Additive 0.05 0.0467 *Parameter estimates for oxypurinol were relative to formation fraction (fm) Estimated allopurinol AUC values varied between 78 and 264 mg/L*h, and estimated oxypurinol AUC values ranged from 10.6 to 71.6 mg/L*h. The target AUC for allopurinol of 43.5mg/L*h was reached in all infants in the hypothermia groups and no-hypothermia group. The target AUC for oxypurinol of 26.5mg/L*h was reached in 66.7% of the infants treated with hypothermia and in 100% of the infants in the no- hypothermia group. In the total group 12 out of 15 patient (80%) reached the target AUC for oxypurinol. Table 4: Proportions of infants who reached the target AUC for allopurinol and oxypurinol in infants treated with hypothermia and those who were not. Target AUC Total group (n=15) Hypothermia (n=9) No-hypothermia (n=6) Allopurinol (43.5 mg/L*h) 100% 100% 100% Oxypurinol (26.5 mg/L*h) 80% 66.7% 100% 9