Kim Annink

159 Allopurinol: old drug, new indication in neonates? Table 1: Continued Study Population Moment of administration and dosages Results Kaandorp et al , 2015 Allopurinol (n=113) vs. placebo (n=111) 500mg allopurinol i.v. antenatally (median allopurinol administration 14min before delivery; IQR=7.3-26.9) In girls S100ß levels and oxidative stress markers are reduced in the allopurinol group compared to controls. No adverse events. Preclinical studies – antenatal administration for HIE Pharmacokinetics of allopurinol in mother and fetus were investigated in case of antenatal allopurinol administration in several experimental studies in fetal sheep. Allopurinol crossed the placenta rapidly in a number of animal studies (52-56). After 20mg/kg allopurinol was administered intravenously the maternal allopurinol and oxypurinol concentrations reached their maximum within 20 minutes after birth in sheep. The oxypurinol concentrations in all fetuses were in the therapeutic range (53). The neuroprotective effect of antenatal allopurinol (20mg/kg weight of the mother) was tested in five sheep and compared to six controls. Allopurinol was administered to the mother during the induction of hypoxia. Brain damage was studied based on histology 48 hours after birth. In this experiment, there was less hippocampal damage in the allopurinol group compared to the placebo group. The dentate gyrus and thalami also appeared to be less damaged based on histological confirmed neuronal necrosis, although this was not statistically significant (57). Moreover, the cardioprotective effect of 20mg/kg allopurinol compared to placebo was also investigated in these 11 sheep after inducing hypoxia with a cord clamp model (53). The allopurinol treated sheep had less cardiac oxidative stress based on fetal blood pressure, heart rate, T/QRS ratio of the fetal electrocardiography and troponin levels. Furthermore, umbilical blood flow was preserved in the allopurinol treated animals, while this was not the case in the control group. These findings suggested a cardioprotective effect of allopurinol in sheep (53). Importantly, core body temperature was not measured, so the influence of hypothermia is unclear in this study. Another study group found a reduced oxygen radical production in 3 fetal sheep after the administration of 400mg allopurinol to the dam (55). Superoxide production was determined with chemiluminescence. The concentrations of superoxide rose until the administration of allopurinol, afterwards it declined until 7