Related Experiment Video
Updated: Jul 18, 2025

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Maturation of Paracetamol Elimination Routes in Preterm Neonates Born Below 32 Weeks of Gestation
Yunjiao Wu1, Swantje Völler1, Elke H J Krekels1
1Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Purpose:
Despite being off-label, intravenous paracetamol (PCM) is increasingly used to control mild-to-moderate pain in preterm neonates. Here we aim to quantify the maturation of paracetamol elimination pathways in preterm neonates born below 32 weeks of gestation.
Methods:
Datasets after single dose (rich data) or multiple doses (sparse data) of intravenous PCM dose (median (range)) 9 (3-25) mg/kg were pooled, containing 534 plasma and 44 urine samples of PCM and metabolites (PCM-glucuronide, PCM-sulfate, PCM-cysteine, and PCM-mercapturate) from 143 preterm neonates (gestational age 27.7 (24.0-31.9) weeks, birthweight 985 (462-1,925) g, postnatal age (PNA) 5 (0-30) days, current weight 1,012 (462-1,959) g. Population pharmacokinetic analysis was performed using NONMEM® 7.4.
Results:
For a typical preterm neonate (birthweight 985 g; PNA 5 days), PCM clearance was 0.137 L/h, with glucuronidation, sulfation, oxidation and unchanged renal clearance accounting for 5.3%, 73.7%, 16.3% and 4.6%, respectively. Maturational changes in total PCM clearance and its elimination pathways were best described by birthweight and PNA. Between 500-1,500 g birthweight, total PCM clearance increases by 169%, with glucuronidation, sulfation and oxidation clearance increasing by 347%, 164% and 164%. From 1-30 days PNA for 985 g birthweight neonate, total PCM clearance increases by 167%, with clearance via glucuronidation and oxidation increasing by 551%, and sulfation by 69%.
Conclusion:
Birthweight and PNA are the most important predictors for maturational changes in paracetamol clearance and its glucuronidation, sulfation and oxidation. As a result, dosing based on bodyweight alone will not lead to consistent paracetamol concentrations among preterm neonates.
More Related Videos
08:08Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the ex vivo Human Placental Perfusion Model
Published on: June 18, 2013
09:04Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
Published on: September 10, 2018
Related Concept Videos
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Drug Elimination: Non-Renal Routes
Drug Excretion: Miscellaneous Routes
Drug Excretion: Pulmonary and Glandular Routes
Drugs can also be excreted in breast milk, which is crucial for breastfeeding infants. The...
Factors Affecting Drug Response: Overview
Factors Influencing Drug Absorption: Presystemic Elimination