Evidence map›Paper›PMID 38693610›Full record

ArticleCPT: pharmacometrics & systems pharmacology2024

A physiologically-based pharmacokinetic precision dosing approach to manage dasatinib drug-drug interactions.

Christina Kovar, Helena Leonie Hanae Loer, Simeon Rüdesheim, Laura Maria Fuhr, Fatima Zahra Marok, Dominik Selzer, Matthias Schwab, Thorsten Lehr

Open access · goldAbstract read
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2024. 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
2.7field-weighted citation impact, top 10% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
  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

8 authors at 2 institutions in 1 country.

Christina KovarClinical Pharmacy, Saarland University, Saarbrücken, Germany.ORCID 0000-0003-0155-9861
Helena Leonie Hanae LoerClinical Pharmacy, Saarland University, Saarbrücken, Germany.
Simeon RüdesheimClinical Pharmacy, Saarland University, Saarbrücken, Germany.ORCID 0000-0002-5741-2511
Laura Maria FuhrClinical Pharmacy, Saarland University, Saarbrücken, Germany.
Fatima Zahra MarokClinical Pharmacy, Saarland University, Saarbrücken, Germany.
Dominik SelzerClinical Pharmacy, Saarland University, Saarbrücken, Germany.ORCID 0000-0002-4126-0816
Matthias SchwabDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.ORCID 0000-0002-9984-075X
Thorsten LehrClinical Pharmacy, Saarland University, Saarbrücken, Germany.ORCID 0000-0002-8372-1465
Saarland University · DEDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · DE

Funding

European Horizon 101057639
6 · The paper itself

Abstract

Dasatinib, a second-generation tyrosine kinase inhibitor, is approved for treating chronic myeloid and acute lymphoblastic leukemia. As a sensitive cytochrome P450 (CYP) 3A4 substrate and weak base with strong pH-sensitive solubility, dasatinib is susceptible to enzyme-mediated drug-drug interactions (DDIs) with CYP3A4 perpetrators and pH-dependent DDIs with acid-reducing agents. This work aimed to develop a whole-body physiologically-based pharmacokinetic (PBPK) model of dasatinib to describe and predict enzyme-mediated and pH-dependent DDIs, to evaluate the impact of strong and moderate CYP3A4 inhibitors and inducers on dasatinib exposure and to support optimized dasatinib dosing. Overall, 63 plasma profiles from perorally administered dasatinib in healthy volunteers and cancer patients were used for model development. The model accurately described and predicted plasma profiles with geometric mean fold errors (GMFEs) for area under the concentration-time curve from the first to the last timepoint of measurement (AUC

Indexed as

Cytochrome P-450 CYP3A InhibitorsDasatinibDrug InteractionsModels, BiologicalProtein Kinase InhibitorsAdultAntineoplastic AgentsArea Under CurveCytochrome P-450 CYP3ACytochrome P-450 CYP3A InducersFemaleHumansMaleMiddle AgedAntineoplastic AgentsCYP3A4 protein, humanCytochrome P-450 CYP3ACytochrome P-450 CYP3A InducersCytochrome P-450 CYP3A InhibitorsDasatinibProtein Kinase Inhibitors

Identifiers

PMID38693610
PMCPMC11247110
OpenAlexW4396596250

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.