Ethanol Pharmacokinetics in Neonates and Infants

Abstract

IntroductionEthanol has been used for years in neonatal and infant liquid medications, yet the pharmacokinetics, pharmacodynamics, and safety of ethanol in this vulnerable population have not been well characterized. The purpose of this review is to raise awareness of ethanol use as an excipient in neonatal and infant medications and to provide insight, based on the available evidence, into clearance rates of ethanol in babies. We also discuss ethanol pharmacokinetics in adults, theoretical pharmacokinetic changes in neonates and infants as it may apply to ethanol disposition, and case reports involving ethanol exposure in neonates and infants.Materials and methodsThis study was a narrative review in which relevant papers were selected using databases and scientific search engines such as PubMed with the key words ethanol, infant, and newborninfant.ResultsIt remains unclear what ethanol exposure is safe for neonates and infants. The Food and Drug Administration and American Academy of Pediatrics have both taken action, by either setting limits of ethanol content in over-the-counter medications or by recommending restricted exposure to ethanol-containing pediatric formulations.ConclusionsUntil the short- and long-term health effects of chronic ethanol administration can be further characterized, ethanol-containing medications should be used with caution.

Central Venous Access in the Pediatric Population With Emphasis on Complications and Prevention Strategies

“…The dosing of ethanol is dependent on the intraluminal volume of the catheter. The American Academy of Pediatrics guidelines on the use of ethanol in pediatric drugs recommend that they should not be able to produce a blood concentration >25 mg/100 mL, which is equivalent to a blood alcohol concentration of 0.025% after a single dose 90 . The maximum predicted distributed blood alcohol concentration of a 5‐kg infant receiving an intravenous bolus of 1.5 mL of 70% ethanol is 0.024%.…”

Neonatal ethanol exposure from ethanol-based hand sanitisers in isolettes

“…According to more recent 2014 guidance of the European Medicines Agency (EMA), blood alcohol levels in children less than 6 years old should not exceed 1 mg/dL, corresponding to a dose of 6 mg/kg 27. The mechanism for ethanol clearance is not well developed in infants; the above-mentioned limit is intended to serve as a safety standard, and is not based on any specific scientific evidence 28. Based on our experiment, a 10 s EBHS hand rub would expose a 2 kg infant to 0.92 mg ethanol.…”

“…For neonates, one area where ethanol exposures have been addressed is in the guidelines for ethanol when used as an excipient in liquid formulations of medications for infants. The American Academy of Pediatrics Committee on Drug26 and the European Medicines Agency27 both have recommended limits on alcohol content in medications for children 28. As per the 1984 guidance of American Academy of Pediatrics, ethanol levels in a child’s blood should not exceed 25 mg/dL after a single dose of medication26; the corresponding maximum ethanol content in a single dose of 150 mg/kg.…”

Neonatal abstinence syndrome: Pharmacologic strategies for the mother and infant

“…extrinsic), the pharmacodynamic and safety profile of ethanol in neonates has not well defined. 44 A pharmacokinetic model of buprenorphine in infants with NAS has been generated. 45 This can serve as the basis of modeling and simulation to optimize dose and dose schedules that takes into account developmental ontogeny of metabolic processes and the natural history of symptom resolution in NAS.…”