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|Title:||Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour|
van Den Broek, M.
van Elburg, R.
van Bel, F.
De Haan, T.
De Boer, I.
|Citation:||Archives of Disease in Childhood: Fetal and Neonatal Edition, 2014; 99(2):F144-F148|
|Publisher:||BMJ Publishing Group|
|J J Kaandorp, M P H van den Broek, M J N L Benders, M A Oudijk, M M Porath, S Bambang Oetomo, M G A J Wouters, Ruurd van Elburg, M T M Franssen, A F Bos, B W J Mol, G H A Visser, F van Bel, C M A Rademaker, J B Derks, for the ALLO-trial Study Group|
|Abstract:||OBJECTIVE: Perinatal hypoxia-induced free radical formation is an important cause of hypoxic-ischaemic encephalopathy and subsequent neurodevelopmental disabilities. Allopurinol reduces the formation of free radicals, which potentially limits hypoxia-induced brain damage. We investigated placental transfer and safety of allopurinol after maternal allopurinol treatment during labour to evaluate its potential role as a neuroprotective agent in suspected fetal hypoxia. DESIGN: We used data from a randomised, double-blind multicentre trial comparing maternal allopurinol versus placebo in case of imminent fetal hypoxia (NCT00189007). PATIENTS: We studied 58 women in labour at term, with suspected fetal hypoxia prompting immediate delivery, in the intervention arm of the study. SETTING: Delivery rooms of 11 Dutch hospitals. INTERVENTION: 500 mg allopurinol, intravenously to the mother, immediately prior to delivery. MAIN OUTCOME MEASURES: Drug disposition (maternal plasma concentrations, cord blood concentrations) and drug safety (maternal and fetal adverse events). RESULTS: Within 5 min after the end of maternal allopurinol infusion, target plasma concentrations of allopurinol of ≥2 mg/L were present in cord blood. Of all analysed cord blood samples, 95% (52/55) had a target allopurinol plasma concentration at the moment of delivery. No adverse events were observed in the neonates. Two mothers had a red and/or painful arm during infusion. CONCLUSIONS: A dose of 500 mg intravenous allopurinol rapidly crosses the placenta and provides target concentrations in 95% of the fetuses at the moment of delivery, which makes it potentially useful as a neuroprotective agent in perinatology with very little side effects. TRIAL REGISTRATION: The study is registered in the Dutch Trial Register (NTR1383) and the Clinical Trials protocol registration system (NCT00189007).|
|Keywords:||ALLO-trial Study Group; Fetal Blood; Fetus; Placenta; Hypoxia-Ischemia, Brain; Free Radicals; Allopurinol; Neuroprotective Agents; Free Radical Scavengers; Double-Blind Method; Pregnancy; Labor, Obstetric; Maternal-Fetal Exchange; Infant, Newborn; Fetal Hypoxia|
|Rights:||Copyright status unknown|
|Appears in Collections:||Obstetrics and Gynaecology publications|
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