title: Essential medicines containing ethanol elevate blood acetaldehyde concentrations in neonates.
abstract: Neonates administered ethanol-containing medicines are potentially at risk of dose-dependent injury through exposure to ethanol and its metabolite, acetaldehyde. Here, we determine blood ethanol and acetaldehyde concentrations in 49 preterm infants (median birth weight = 1190 g) dosed with iron or furosemide, medicines that contain different amounts of ethanol, and in 11 control group infants (median birth weight = 1920 g) who were not on any medications. Median ethanol concentrations in neonates administered iron or furosemide were 0.33 (range = 0-4.92) mg/L, 0.39 (range = 0-72.77) mg/L and in control group infants were 0.15 (range = 0.03-5.4) mg/L. Median acetaldehyde concentrations in neonates administered iron or furosemide were 0.16 (range = 0-8.89) mg/L, 0.21 (range = 0-2.43) mg/L and in control group infants were 0.01 (range = 0-0.14) mg/L. There was no discernible relationship between blood ethanol or acetaldehyde concentrations and time after medication dose.
  
  
  CONCLUSIONS
  Although infants dosed with iron or furosemide had low blood ethanol concentrations, blood acetaldehyde concentrations were consistent with moderate alcohol exposure. The data suggest the need to account for the effects of acetaldehyde in the benefit-risk analysis of administering ethanol-containing medicines to neonates.
  
  
  BACKGROUND
  • Neonates are commonly treated with ethanol-containing medicines, such as iron and furosemide. • However, there is no data on whether this leads to appreciable increases in blood concentrations of ethanol or its metabolite, acetaldehyde. What is New: • In this study, we find low blood ethanol concentrations in neonates administered iron and/or furosemide but markedly elevated blood acetaldehyde concentrations in some infants receiving these medicines. • Our data suggest that ethanol in drugs may cause elevation of blood acetaldehyde, a potentially toxic metabolite.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester, LE1 9HN, UK. hp28@le.ac.uk.
authors.forename: H C
authors.identifier: http://orcid.org/0000-0003-0514-2529
authors.initials: HC
authors.lastname: Pandya
authors.affiliation: Department of Pharmacy, University of Hospitals Leicester NHS Trust, Leicester, UK.
authors.forename: H
authors.initials: H
authors.lastname: Mulla
authors.affiliation: Neonatal Unit University of Hospitals Leicester NHS Trust, Leicester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Hubbard
authors.affiliation: Department of Chemistry, University of Leicester, Leicester, UK.
authors.forename: R L
authors.initials: RL
authors.lastname: Cordell
authors.affiliation: Department of Chemistry, University of Leicester, Leicester, UK.
authors.forename: P S
authors.initials: PS
authors.lastname: Monks
authors.affiliation: Department of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: S
authors.initials: S
authors.lastname: Yakkundi
authors.affiliation: Department of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: McElnay
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Nunn
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Turner
mesh_terms: D000079:Acetaldehyde / Q000097:blood*; D016022:Case-Control Studies; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood*; D005665:Furosemide / Q000008:administration & dosage* / Q000737:chemistry; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D058085:Iron Compounds / Q000008:administration & dosage* / Q000737:chemistry; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000009:adverse effects*
chemical_list: D058085:Iron Compounds; D049994:Sodium Potassium Chloride Symporter Inhibitors; D000431:Ethanol; D005665:Furosemide; D000079:Acetaldehyde
keywords: Alcohol; Drug excipients; Infants