Evidence map›Paper›PMID 36369327›Full record

ArticleClinical pharmacokinetics2022

Feasibility of a Pragmatic PBPK Modeling Approach: Towards Model-Informed Dosing in Pediatric Clinical Care.

Joyce E M van der Heijden, Jolien J M Freriksen, Marika A de Hoop-Sommen, Lianne P M van Bussel, Sander H P Driessen, Anne E M Orlebeke, Laurens F M Verscheijden, Rick Greupink, Saskia N de Wildt

Abstract read
In one paragraph

Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Optimization of pediatric dosing regimens for aztreonam and amoxicillin/clavulanate combination therapy against multidrug-resistant bacteria.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
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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

9 authors.

Joyce E M van der HeijdenDepartment of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands. Joyce.vanderHeijden@radboudumc.nl.ORCID http://orcid.org/0000-0002-3584-2318
Jolien J M FreriksenDepartment of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0002-4114-5412
Marika A de Hoop-SommenDepartment of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0003-1923-2111
Lianne P M van BusselDepartment of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Sander H P DriessenDepartment of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Anne E M OrlebekeDepartment of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Laurens F M VerscheijdenDepartment of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0003-0303-898X
Rick Greupink *Department of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0003-2599-7540
Saskia N de Wildt *Department of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.ORCID http://orcid.org/0000-0002-0502-0647

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveMore than half of all drugs are still prescribed off-label to children. Pharmacokinetic (PK) data are needed to support off-label dosing, however for many drugs such data are either sparse or not representative. Physiologically-based pharmacokinetic (PBPK) models are increasingly used to study PK and guide dosing decisions. Building compound models to study PK requires expertise and is time-consuming. Therefore, in this paper, we studied the feasibility of predicting pediatric exposure by pragmatically combining existing compound models, developed e.g. for studies in adults, with a pediatric and preterm physiology model.

methodsSeven drugs, with various PK characteristics, were selected (meropenem, ceftazidime, azithromycin, propofol, midazolam, lorazepam, and caffeine) as a proof of concept. Simcyp

resultsOverall, model predicted PK in infants, children and adolescents capture clinical data. Confidence in PBPK model performance was therefore considered high. Predictive performance tends to decrease when predicting PK in the (pre)term neonatal population.

conclusionPragmatic PBPK modeling in pediatrics, based on compound models verified with adult data, is feasible. A thorough understanding of the model assumptions and limitations is required, before model-informed doses can be recommended for clinical use.

Indexed as

Models, BiologicalPropofolAdolescentAdultChildComputer SimulationHumansInfantInfant, NewbornMidazolamMidazolamPropofol

Identifiers

PMID36369327
PMCPMC9651907

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Registered trials

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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.