Evidence map›Paper›PMID 40040359›Full record

ArticleBritish journal of clinical pharmacology2025

Paracetamol and its metabolites in children and adults with spinal muscular atrophy - a population pharmacokinetic model.

Qiaolin Zhao, Marie Mostue Naume, Brenda C M de Winter, Thomas Krag, Sissel Sundell Haslund-Krog, Karoline Lolk Revsbech, John Vissing, Helle Holst, Morten Hylander Møller, Tessa Munkeboe Hornsyld and 5 more

Abstract read
In one paragraph

Article in British journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Qiaolin ZhaoDepartment of Hospital Pharmacy, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID https://orcid.org/0009-0008-5800-0966
Marie Mostue NaumeCopenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Brenda C M de WinterDepartment of Hospital Pharmacy, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID https://orcid.org/0000-0002-4452-8443
Thomas KragCopenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Sissel Sundell Haslund-KrogDepartment of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark.ORCID https://orcid.org/0000-0001-9003-7816
Karoline Lolk RevsbechCopenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
John VissingCopenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Helle HolstRare disease and advance therapies, Novo Nordisk, Denmark.
Morten Hylander MøllerDepartment of Clinical Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
Tessa Munkeboe HornsyldCopenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Morten DunøDepartment of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Christina Engel Hoei-HansenDepartment of Clinical Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
Alfred Peter BornDepartment of Pediatric and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Per Bo JensenDepartment of Clinical Biochemistry, Bispebjerg Hospital, Copenhagen, Denmark.
Mette Cathrine ØrngreenCopenhagen Neuromuscular Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Funding

Elsass Foundation 18-3-0451
6 · The paper itself

Abstract

aimsThe aim of the study was to investigate whether differences in paracetamol pharmacokinetics (PK) between spinal muscular atrophy (SMA) patients and healthy controls (HC) could be attributed to specific clinical covariates.

methodsNonlinear mixed-effects modelling (NONMEM 7.4) was used to develop a population PK model, explore covariates for paracetamol and its metabolites and perform simulations.

resultsWith body weight as allometric scaling in the model, SMA disease resulted in a 58% (95% confidence interval [CI]: 20%-130%) increase in the volume of distribution for paracetamol and its metabolites compared to healthy controls. Decreased plasma myoglobin and plasma bilirubin concentrations, seen in SMA patients, resulted in a higher paracetamol leftover clearance (SMA, median: 13.30 L/h/70 kg, 95% CI: 9.14-18.29%; HC, median: 4.05 L/h/70 kg, 95% CI: 3.38-8.83%) and a shift from slower sulfate formation clearance (SMA, median: 8.78 L/h/70 kg, 95% CI: 7.22-9.61%; HC, median: 9.30 L/h/70 kg, 95% CI: 8.42-10.15%) and faster oxidative metabolites elimination clearance (SMA, median: 3.74 L/h/70 kg, 95% CI: 3.31-4.72%; HC, median: 3.25 L/h/70 kg, 95% CI: 2.87-3.92%). Simulations revealed that in SMA patients, higher bodyweight was associated with increased exposure to paracetamol and its metabolites.

conclusionsThe differences in PK between SMA patients and healthy controls could be explained by body weight and the disease itself. SMA patients should be dosed cautiously, ensuring doses do not exceed the recommended body weight adjusted limit.

Indexed as

AcetaminophenAnalgesics, Non-NarcoticModels, BiologicalMuscular Atrophy, SpinalAdolescentAdultBilirubinBody WeightCase-Control StudiesChildChild, PreschoolComputer SimulationFemaleHumansInfantMaleAcetaminophenAnalgesics, Non-NarcoticBilirubinmetabolitesparacetamolpharmacokineticSMA

Identifiers

PMID40040359
PMCPMC12199096

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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.