Kim Annink

162 Chapter 7 effect of allopurinol in infants with HLHS. However, when the outcome parameters were analyzed separately, there were no significant differences. Allopurinol was not effective in other congenital heart diseases (65). The authors hypothesized that HLHS infants had a worse cerebral oxygenation status before surgery than infants with other congenital heart diseases, but this has not been confirmed (65). Marro et al. investigated the effect of allopurinol in neonates undergoing extracorporeal membrane oxygenation (ECMO) in a RCT. Allopurinol was given to 11 infants in a dose of 10mg/kg before surgery, 20mg/kg was added to the ECMO circulation and afterwards 5mg/kg was given every 8 hours for 72 hours. Fourteen infants received placebo. This study confirmed that uric acid levels are decreased after allopurinol administration and hypoxanthine levels are increased, suggesting that the xanthine-oxidase pathway was inhibited and consequently the formation of free radicals was possibly reduced. The neuroprotective effect of allopurinol could not be verified, because free radicals and neurological outcome were not determined (66). In premature born babies, the anti-oxidant system is not fully mature yet, thereby increasing the risk of free radical formation during stress. Therefore, idiopathic respiratory distress syndrome (IRDS) was believed to be caused by free radical formation (67). A study in 1984 suggested a positive effect on mortality in preterm babies with IRDS (67). Later, allopurinol was also tested in premature born babies with a gestational age of 27 to 31 weeks (oral allopurinol 20mg/kg: n=16, placebo: n=17). In this insufficiently powered study, allopurinol had no effect on the incidence of periventricular leukomalacia, periventricular hemorrhage, porencephaly, necrotic enterocolitis, retinopathy of prematurity or bronchopulmonary dysplasia (68). Pharmacokinetics of allopurinol in neonates A combined pharmacokinetic study was performed for the cohorts of van Bel et al. and Benders et al. Almost all neonates reached the target levels (2-13.6μg/ml) after two dosages of 20mg/kg, most of them even reached supra-therapeutic levels. Oxypurinol concentrations could be measured within 1 hour after the first dose of allopurinol. Oxypurinol levels were high for at least 14 hours after a first dose. The half-life of allopurinol was estimated around 7 hours (69). In infants with HLHS the half-life of allopurinol was shorter, around 2.5 hours (64). This difference might be explained by the younger age of the infants with HIE (69). Despite the supra-