Evidence map›Paper›PMID 36401151›Full record

ArticleClinical pharmacokinetics2022

Physiologically Based Modelling Framework for Prediction of Pulmonary Pharmacokinetics of Antimicrobial Target Site Concentrations.

Linda B S Aulin, Sebastian T Tandar, Torben van Zijp, Etienne van Ballegooie, Piet H van der Graaf, Mohammed A A Saleh, Pyry Välitalo, J G Coen van Hasselt

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 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
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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

8 authors.

Linda B S AulinLeiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. l.b.s.aulin@lacdr.leidenuniv.nl.ORCID http://orcid.org/0000-0003-4840-5704
Sebastian T TandarLeiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-9255-2456
Torben van ZijpLeiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.ORCID http://orcid.org/0000-0001-6831-4565
Etienne van BallegooieLeiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Piet H van der GraafLeiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Mohammed A A SalehLeiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-0517-6051
Pyry VälitaloUniversity of Eastern Finland, Kuopio, Finland.
J G Coen van HasseltLeiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. coen.vanhasselt@lacdr.leidenuniv.nl.ORCID http://orcid.org/0000-0002-1664-7314

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesPrediction of antimicrobial target-site pharmacokinetics is of relevance to optimize treatment with antimicrobial agents. A physiologically based pharmacokinetic (PBPK) model framework was developed for prediction of pulmonary pharmacokinetics, including key pulmonary infection sites (i.e. the alveolar macrophages and the epithelial lining fluid).

methodsThe modelling framework incorporated three lung PBPK models: a general passive permeability-limited model, a drug-specific permeability-limited model and a quantitative structure-property relationship (QSPR)-informed perfusion-limited model. We applied the modelling framework to three fluoroquinolone antibiotics. Incorporation of experimental drug-specific permeability data was found essential for accurate prediction.

resultsIn the absence of drug-specific transport data, our QSPR-based model has generic applicability. Furthermore, we evaluated the impact of drug properties and pathophysiologically related changes on pulmonary pharmacokinetics. Pulmonary pharmacokinetics were highly affected by physiological changes, causing a shift in the main route of diffusion (i.e. paracellular or transcellular). Finally, we show that lysosomal trapping can cause an overestimation of cytosolic concentrations for basic compounds when measuring drug concentrations in cell homogenate.

conclusionThe developed lung PBPK model framework constitutes a promising tool for characterization of pulmonary exposure of systemically administrated antimicrobials.

Indexed as

Anti-Infective AgentsModels, BiologicalHumansLungPharmacokineticsAnti-Infective Agents

Identifiers

PMID36401151
PMCPMC9676785

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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.