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.

Conclusion: 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.

What is known: • 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.

Keywords: Alcohol; Drug excipients; Infants.

Fig. 1

Blood concentrations of ethanol (a,c) and acetaldehyde (b,d) plotted against time. Blood concentrations are related to dosing with iron (a,b) or furosemide (c,d) according to the medication the child received prior to blood sampling. There is no discernible correlation between blood ethanol (white circle and black circle) or blood acetaldehyde (white triangle and black triangle) concentrations and time after administration of iron or furosemide

Fig. 2

Plots of blood ethanol vs. blood acetaldehyde concentrations in neonates receiving iron and/or furosemide. Blood concentrations are related to dosing with iron (a) or furosemide (b) according to the medication the child received prior to blood sampling. For both iron and furosemide groups, there was a weak but significant correlation between blood ethanol and blood acetaldehyde concentrations. Pearson product moment coefficient, R ² = 0.05 and R ² = 0.34 for iron and furosemide groups, respectively, P < 0.01 for both