Evidence map›Paper›PMID 30321459›Full record

Observational studyBritish journal of clinical pharmacology2019

Population pharmacokinetic modelling of intravenous paracetamol in fit older people displays extensive unexplained variability.

P Mian, M J van Esdonk, K T Olkkola, B C M de Winter, A Liukas, I Spriet, D Tibboel, M Petrovic, B C P Koch, K Allegaert

Open access · bronzeAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 19% of its field
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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Observational
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

10 authors at 7 institutions in 3 countries.

P MianIntensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.ORCID 0000-0002-3551-1201
M J van EsdonkDivision of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
K T OlkkolaDepartment of Anaesthesiology, Intensive Care and Pain Medicine University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
B C M de WinterDepartment of Hospital Pharmacy, Erasmus MC, Rotterdam, The Netherlands.
A LiukasDepartment of Anaesthesiology, Turku University Hospital, Turku, Finland.
I SprietClinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven and Pharmacy Department, University Hospital Leuven, Leuven, Belgium.
D TibboelIntensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.
M PetrovicDepartment of Geriatrics, Ghent University Hospital, Ghent, Belgium.
B C P KochDepartment of Hospital Pharmacy, Erasmus MC, Rotterdam, The Netherlands.
K AllegaertIntensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.ORCID 0000-0001-9921-5105
Erasmus MC - Sophia Children’s Hospital · NLErasmus MC · NLGhent University Hospital · BEKU Leuven · BELeiden University · NLTurku University Hospital · FIUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsParacetamol is the analgesic most used by older people. The physiological changes occurring with ageing influence the pharmacokinetics (PK) of paracetamol and its variability. We performed a population PK-analysis to describe the PK of intravenous (IV) paracetamol in fit older people. Simulations were performed to illustrate target attainment and variability of paracetamol exposure following current dosing regimens (1000 mg every 6 h, every 8 h) using steady-state concentration (C

methodsA population PK-analysis, using NONMEM 7.2, was performed based on 601 concentrations of paracetamol from 30 fit older people (median age 77.3 years, range [61.8-88.5], body weight 79 kg [60-107]). All had received an IV paracetamol dose of 1000 mg (over 15 min) after elective knee surgery.

resultsA two-compartment PK-model best described the data. Volume of distribution of paracetamol increased exponentially with body weight. Clearance was not influenced by any covariate. Simulations of the standardized dosing regimens resulted in a C

conclusionsThe target concentration was achieved in the average patient with 1000 mg every 6 h, while every 8 h resulted in underdosing for the majority of the population. Furthermore, due to a large (unexplained) interindividual variability in paracetamol PK a relevant proportion of the fit older people remained either under- or over exposed.

Indexed as

Biological Variation, PopulationModels, BiologicalAcetaminophenAgedAged, 80 and overAge FactorsAnalgesiaAnalgesics, Non-NarcoticDose-Response Relationship, DrugFemaleHumansInfusions, IntravenousMaleMiddle AgedAcetaminophenAnalgesics, Non-Narcoticacetaminophenagingelderlygeriatricpharmacokineticsvariability

Identifiers

PMID30321459
PMCPMC6303215
OpenAlexW2896641668

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

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.