Related Experiment Video

Updated: Jun 3, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

7.8K

Urinary Acetaminophen Metabolites and Clinical Outcomes in Extremely Premature Infants

Miguel Guardado1, Dara Torgerson2, Cheryl Chapin3

  • 1Department of Biological and Medical Informatics, University of California, San Francisco, San Francisco, California.

American Journal of Perinatology
|January 9, 2025
PubMed

Insights

Acetaminophen (APAP) use in premature infants was studied. Urinary APAP metabolite levels were measured, but no association was found with bronchopulmonary dysplasia or retinopathy of prematurity risk.

Area of Science:

  • Neonatal Medicine
  • Pharmacology
  • Toxicology

Background:

  • Acetaminophen (APAP) is used for pain and patent ductus arteriosus in extremely premature infants.
  • High-dose APAP is toxic in adults, and prior studies suggest APAP metabolites in breast milk may link to infant BPD and ROP.
  • The safety and metabolite levels of APAP in this vulnerable population require further investigation.

Purpose of the Study:

  • To determine the levels of APAP metabolites in the urine of extremely premature infants at high risk for BPD and ROP.
  • To examine the association between APAP metabolite levels and the development of BPD and ROP in these infants.

Main Methods:

  • Urine samples from 314 infants (<29 weeks' gestation) from the TOLSURF and PROP studies were analyzed using untargeted UHPLC:MS/MS.
  • Multivariate logistic regression and meta-analysis were employed to assess the relationship between APAP metabolite levels and clinical outcomes.

Main Results:

  • The primary urinary APAP metabolite, 4-APAP sulfate, was detected in 95% of samples and correlated with other metabolites.
  • Elevated 4-APAP sulfate levels and duration were higher in infants transitioning from parenteral to enteral nutrition.
  • No significant associations were found between APAP metabolite levels and BPD or ROP on days 10 and 28.

Conclusions:

  • Urinary APAP metabolite levels were not associated with an increased risk of BPD or ROP in extremely premature infants.
  • The safety of APAP in this population remains to be fully established.
  • Further research is needed to understand APAP metabolism and its long-term effects in neonates.

More Related Videos

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale19:15

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

Published on: August 25, 2014

85.8K
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats07:36

Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats

Published on: November 20, 2015

11.3K

Related Concept Videos

Factors Affecting Drug Response: Overview01:21

Factors Affecting Drug Response: Overview

When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
1.8K
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
80
Phase II Reactions: Acetylation Reactions01:24

Phase II Reactions: Acetylation Reactions

Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
174
Drug Elimination by Renal Route: Tubular Reabsorption01:22

Drug Elimination by Renal Route: Tubular Reabsorption

During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. However, the majority of drugs are either weak acids or weak bases, and their ionization level is dependent on pH. By altering the pH of urine, the...
3.2K
Enhanced Elimination of Poison01:26

Enhanced Elimination of Poison

Poison can be effectively removed from the gastrointestinal (GI) tract through various decontamination procedures.
Antidotes serve a crucial role in counteracting the effects of poison by inhibiting enzymes responsible for producing harmful drug metabolites. In some cases, these toxic metabolites can be neutralized by endogenous cosubstrates, which are maintained at specific concentrations to prevent interaction with cellular macromolecules and subsequent cell death.
Renal excretion is the...
473
Factors Influencing Drug Absorption: Presystemic Elimination01:24

Factors Influencing Drug Absorption: Presystemic Elimination

The pharmacokinetic journey of oral drugs begins with a crucial first pass through the hepatic portal system, called the first-pass effect. This first pass significantly impacts bioavailability — the proportion of a drug that enters systemic circulation and is available for therapeutic action. The primary route sees the drug absorbed by intestinal membranes and then shunted to the liver via the hepatic portal vein. Here, pre-systemic elimination occurs as drugs face metabolism or biliary...
176