Kim Annink

163 Allopurinol: old drug, new indication in neonates? therapeutic allopurinol and oxypurinol concentrations in neonates with HIE, no adverse events were seen (46,47). In the allopurinol treated infants undergoing ECMO, peak serum levels of allopurinol and oxypurinol were 28.4±3.5μg/ml and 15±4μg/ml respectively (70). The allopurinol and oxypurinol levels in ECMO were even higher than in the HIE studies. This is probably caused by the higher dose and frequency of allopurinol administration compared to the previously mentioned cohorts (69,70) Pharmacokinetics were also studied in 24 mothers delivering full-term neonates and 44 mothers delivering preterm neonates. Allopurinol (500mg) was orally administered to all mothers during early labor. All mothers reached therapeutic allopurinol levels and the levels of allopurinol in the cord blood and in the newborn at 24 hours after birth were therapeutic. Therapeutic levels in cord blood were reached as soon as 23 minutes after allopurinol administration, suggesting a quick placental transfer of oral allopurinol (52). In the antenatal pharmacokinetic study of Kaandorp et al. , 95% of the infants had an allopurinol concentration above the target concentrations in the cord blood (allopurinol ≥ 2 μg/ml and oxypurinol ≥ 4 μg/ml). The target concentrations were reached within 5 minutes after the end of maternal allopurinol infusion (71). In the ALLO-trial, 72% of the pregnant women reached the target blood levels of allopurinol (59). Safety In adults, a potentially fatal side effect of allopurinol is the allopurinol hypersensitivity reaction (AHR). This AHR is thought to be caused by potentially immunogenic complexes of oxypurinol and certain human leukocyte antigen (HLA) proteins, particularly HLA-B*58:01 (which is more common in Asians than in Caucasians, similar to the frequency distribution of AHR). AHR predominantly affects the skin and may present as a generalized rash, but can also present as severe exfoliative skin reaction, i.e. as Stevens-Johnson syndrome or toxic epidermal necrolysis. AHR might also present with eosinophilia, leukocytosis, fever, acute hepatocellular injury and/or progressive kidney failure (1). Most AHR have been diagnosed after daily administration of allopurinol for a duration of more than 2 to 3 weeks, but single cases have been reported after a single day of 7