Trial reportJournal of clinical pharmacology2014
Population pharmacokinetics of paracetamol across the human age-range from (pre)term neonates, infants, children to adults.
Trial report in Journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Paracetamol (acetaminophen) for prevention or treatment of pain in newborns.The Cochrane database of systematic reviews · 2020Pooled it
- Paracetamol (acetaminophen) for prevention or treatment of pain in newborns.The Cochrane database of systematic reviews · 2016Pooled it
- Randomized Population Pharmacokinetic Analysis and Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and Infants.Journal of clinical pharmacology · 2020Trial
- Successful Use of [Clinical pharmacokinetics · 2017Trial
- Exposure to acetaminophen and all its metabolites upon 10, 15, and 20 mg/kg intravenous acetaminophen in very-preterm infants.Pediatric research · 2017Trial
- Population pharmacokinetics of intravenous acetaminophen in Japanese patients undergoing elective surgery.Journal of anesthesia · 2017Trial
- Trial
- Trial
- Pharmacological therapy of neonatal analgosedation: current status, dilemmas, and perspectives.Frontiers in pediatrics · 2026Review
- A Novel Maturation Equation for Hepatic Clearance Across Preterm, Term Neonates, Children, and Adults: Application to Paracetamol and Its Metabolite.Journal of clinical pharmacology · 2025Article
- Global research on the utilization of population pharmacokinetic model: a bibliometric analysis from 2000 to 2024.Frontiers in pharmacology · 2025Review
- Effect of Nutrition on Drug-Induced Liver Injury: Insights from a High-Fat Diet Mouse Model.Turkish journal of pharmaceutical sciences · 2024Article
- The Use of Population Pharmacokinetics to Extrapolate Food Effects from Human Adults and Beagle Dogs to the Pediatric Population Illustrated with Paracetamol as a Test Case.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Maturation of Paracetamol Elimination Routes in Preterm Neonates Born Below 32 Weeks of Gestation.Pharmaceutical research · 2023Article
- Pharmacokinetic and pharmacodynamic principles: unique considerations for optimal design of neonatal clinical trials.Frontiers in pediatrics · 2023Review
- Pharmacokinetics of acetaminophen after a single Oral administration of 20 or 40 mg/kg to 7-9 Day-old foals.Frontiers in veterinary science · 2023Article
- Potential implications of DMET ontogeny on the disposition of commonly prescribed drugs in neonatal and pediatric intensive care units.Expert opinion on drug metabolism & toxicology · 2021Review
- Population Pharmacokinetic Modeling of Acetaminophen Protein Adducts in Adults and Children.Journal of clinical pharmacology · 2020Article
- Phase I Pharmacokinetic Study of Fixed-Dose Combinations of Ibuprofen and Acetaminophen in Healthy Adult and Adolescent Populations.Drugs in R&D · 2020Article
- Electronic Health Record-Embedded Decision Support Platform for Morphine Precision Dosing in Neonates.Clinical pharmacology and therapeutics · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In order to characterize the variation in pharmacokinetics of paracetamol across the human age span, we performed a population pharmacokinetic analysis from preterm neonates to adults with specific focus on clearance. Concentration-time data obtained in 220 neonates (post-natal age 1-76 days, gestational age 27-42 weeks), infants (0.11-1.33 yrs), children (2-7 yrs) and adults (19-34 yrs) were analyzed using NONMEM 7.2. In the covariate analysis, linear functions, power functions, and a power function with a bodyweight-dependent exponent were tested. Between preterm neonates and adults, linear bodyweight functions were identified for Q2, Q3, V1, V2, and V3, while for CL a power function with a bodyweight-dependent exponent k was identified (CLi = CLp × (BW/70)(k) ). The exponent k was found to decrease in a sigmoidal manner with bodyweight from 1.2 to 0.75, with half the decrease in exponent reached at 12.2 kg. No other covariates such as age were identified. A pharmacokinetic model for paracetamol characterizing changes in pharmacokinetic parameters across the pediatric age-range was developed. Clearance was found to change in a nonlinear manner with bodyweight. Based on the final model, dosing guidelines are proposed from preterm neonates to adolescents resulting in similar exposure across all age ranges.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.