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Type: Journal article
Title: Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour
Author: Kaandorp, J.
van Den Broek, M.
Benders, M.
Oudijk, M.
Porath, M.
Oetomo, S.
Wouters, M.
van Elburg, R.
Franssen, M.
Bos, A.
Mol, B.
Visser, G.
van Bel, F.
Rademaker, C.
Derks, J.
De Haan, T.
Boon, J.
De Boer, I.
Rijnders, R.
Jacobs, C.
et al.
Citation: Archives of Disease in Childhood: Fetal and Neonatal Edition, 2014; 99(2):F144-F148
Publisher: BMJ Publishing Group
Issue Date: 2014
ISSN: 1359-2998
Statement of
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
RMID: 0030023198
DOI: 10.1136/archdischild-2013-304876
Appears in Collections:Obstetrics and Gynaecology publications

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