ArticleClinical pharmacokinetics2014
Pediatric microdose study of [(14)C]paracetamol to study drug metabolism using accelerated mass spectrometry: proof of concept.
Article in Clinical pharmacokinetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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
17 citing papers in PubMed, 32 citations in OpenAlex.
- Successful Use of [Clinical pharmacokinetics · 2017Trial
- Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper.British journal of clinical pharmacology · 2022Review
- Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport.British journal of clinical pharmacology · 2022Review
- The Oral Bioavailability and Metabolism of Midazolam in Stable Critically Ill Children: A Pharmacokinetic Microtracing Study.Clinical pharmacology and therapeutics · 2021Article
- Proof of Concept: First Pediatric [Clinical pharmacology and therapeutics · 2020Article
- Phase 0/microdosing approaches: time for mainstream application in drug development?Nature reviews. Drug discovery · 2020Review
- Innovative Approaches for Pharmacology Studies in Pregnant and Lactating Women: A Viewpoint and Lessons from HIV.Clinical pharmacokinetics · 2020Article
- Dose-linearity of the pharmacokinetics of an intravenous [British journal of clinical pharmacology · 2019Article
- Oral drug absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions.Biopharmaceutics & drug disposition · 2017Review
- Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology.Chemical research in toxicology · 2016Review
- Using Physiologically Based Pharmacokinetic (PBPK) Modelling to Gain Insights into the Effect of Physiological Factors on Oral Absorption in Paediatric Populations.The AAPS journal · 2016Article
- Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development.Clinical and translational science · 2016Review
- Opportunities in low-level radiocarbon microtracing: applications and new technology.Future science OA · 2016Review
- To Apply Microdosing or Not? Recommendations to Single Out Compounds with Non-Linear Pharmacokinetics.Clinical pharmacokinetics · 2016Article
- Use of microdose phenotyping to individualise dosing of patients.Clinical pharmacokinetics · 2015Article
- Observational infant exploratory [(14)C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis.British journal of clinical pharmacology · 2015Observational
- Ethics of drug research in the pediatric intensive care unit.Paediatric drugs · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPediatric drug development is hampered by practical, ethical, and scientific challenges. Microdosing is a promising new method to obtain pharmacokinetic data in children with minimal burden and minimal risk. The use of a labeled oral microdose offers the added benefit to study intestinal and hepatic drug disposition in children already receiving an intravenous therapeutic drug dose for clinical reasons.
objectiveThe objective of this study was to present pilot data of an oral [(14)C]paracetamol [acetaminophen (AAP)] microdosing study as proof of concept to study developmental pharmacokinetics in children.
methodsIn an open-label microdose pharmacokinetic pilot study, infants (0-6 years of age) received a single oral [(14)C]AAP microdose (3.3 ng/kg, 60 Bq/kg) in addition to intravenous therapeutic doses of AAP (15 mg/kg intravenous every 6 h). Blood samples were taken from an indwelling catheter. AAP blood concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and [(14)C]AAP and metabolites ([(14)C]AAP-Glu and [(14)C]AAP-4Sul) were measured by accelerator mass spectrometry.
resultsTen infants (aged 0.1-83.1 months) were included; one was excluded as he vomited shortly after administration. In nine patients, [(14)C]AAP and metabolites in blood samples were detectable at expected concentrations: median (range) maximum concentration (C max) [(14)C]AAP 1.68 (0.75-4.76) ng/L, [(14)C]AAP-Glu 0.88 (0.34-1.55) ng/L, and [(14)C]AAP-4Sul 0.81 (0.29-2.10) ng/L. Dose-normalized oral [(14)C]AAP C max approached median intravenous average concentrations (C av): 8.41 mg/L (3.75-23.78 mg/L) and 8.87 mg/L (3.45-12.9 mg/L), respectively.
conclusionsWe demonstrate the feasibility of using a [(14)C]labeled microdose to study AAP pharmacokinetics, including metabolite disposition, in young children.
Indexed as
Identifiers
What OpenQuestion holds
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.