Kim Annink

197 Pharmacokinetics of allopurinol in the ALBINO trial Figure 1: During acute (fetal) hypoxia, hypoxanthine and xanthine-oxidase levels rise because of primary energy failure and ATP degradation. After birth, during reperfusion, hypoxanthine in combination with oxygen is converted by xanthine-oxidase into xanthine, uric acid and the toxic superoxide. Allopurinol and its active metabolite (oxypurinol) inhibit the conversion of hypoxanthine and oxygen into superoxide. Allopurinol and oxypurinol are eliminated via the kidneys. METHODS Setting and study design (Near-)term patients who fulfilled criteria for perinatal asphyxia (see below) and early signs of evolving encephalopathy and were included in the double blind randomized ALBINO trial received an initial dose of study medication (20 mg/kg allopurinol or placebo, mannitol) intravenously during resuscitation within 45 minutes after birth. The second dose of 10 mg/kg allopurinol or placebo was administered 12 hours after the initial dose in infants who needed therapeutic hypothermia. Patients were eligible for the ALBINO trial if they fulfilled one or more of the criteria for perinatal asphyxia: 1) pH < 7.00 or base deficit ≥ 16 mmol/l, 2) need for ongoing cardiac massage for ≥ 5 min postpartum, 3) need for adrenalin administration during resuscitation, 4) Apgar score ≤5 after 10 min postpartum; in combination with two or more early signs of evolving encephalopathy: 1) altered state of consciousness, 2) hypotonia or hypertonia, 3) absent/insufficient spontaneous respiration requiring 9