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Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour
- Source :
- Kaandorp, J J, van den Broek, M P H, Benders, M J N L, Oudijk, M A, Porath, M M, Oetomo, S B, Wouters, M G A J, van Elburg, R M, Franssen, M T M, Bos, A T, Mol, B W J, Visser, G H A, van Bel, F, Rademaker, C M A & Derks, J B 2014, ' Rapid target allopurinol concentrations in the hypoxic fetus after maternal administration during labour ', Archives of Disease in Childhood-Fetal and Neonatal Edition, vol. 99, no. 2, pp. F144-F148 . https://doi.org/10.1136/archdischild-2013-304876, Archives of Disease in Childhood-fetal and Neonatal Edition, 99(2), F144-F148. BMJ Publishing Group, Archives of disease in childhood. Fetal and neonatal edition, 99(2), F144-F148. BMJ Publishing Group, Archives of Disease in Childhood-Fetal and Neonatal Edition, 99(2), F144-F148. BMJ Publishing Group, ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, 99(2), F144-F148. BMJ PUBLISHING GROUP
- Publication Year :
- 2014
-
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).
- Subjects :
- Adult
XANTHINE-OXIDASE
Free Radicals
Allopurinol
Placenta
Placebo
Fetal Hypoxia
FREE RADICAL PRODUCTION
RATS
BRAIN-DAMAGE
Fetus
Double-Blind Method
Pregnancy
medicine
INJURY
Humans
REPERFUSION
NITRIC-OXIDE SYNTHASE
Adverse effect
Maternal-Fetal Exchange
Labor, Obstetric
PERINATAL ASPHYXIA
business.industry
Neonatal encephalopathy
Infant, Newborn
NEONATAL ENCEPHALOPATHY
Obstetrics and Gynecology
General Medicine
Free Radical Scavengers
medicine.disease
Fetal Blood
Perinatal asphyxia
ISCHEMIA
Neuroprotective Agents
Cord blood
Anesthesia
Pediatrics, Perinatology and Child Health
Hypoxia-Ischemia, Brain
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 13592998
- Volume :
- 99
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Archives of Disease in Childhood-Fetal and Neonatal Edition
- Accession number :
- edsair.doi.dedup.....fb5c06f99c8582d7095125159d139138