Evidence mapPaperPMID 35307978Full record

ArticlePharmacology research & perspectives2022

A physiologically based pharmacokinetic model of clopidogrel in populations of European and Japanese ancestry: An evaluation of CYP2C19 activity.

Janna K Duong, Romina A Nand, Aarti Patel, Oscar Della Pasqua, Annette S Gross

Open access · goldAbstract read
In one paragraph

Article in Pharmacology research & perspectives, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. 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

5 authors at 2 institutions in 3 countries.

Janna K DuongClinical Pharmacology Modelling and Simulation, GlaxoSmithKline R&D, Ermington, Australia.ORCID 0000-0003-2347-7277
Romina A NandClinical Pharmacology Modelling and Simulation, GlaxoSmithKline R&D, Ermington, Australia.ORCID 0000-0002-3253-0909
Aarti PatelDrug Metabolism and Pharmacokinetics, GlaxoSmithKline R&D, Stevenage, UK.
Oscar Della PasquaClinical Pharmacology Modelling and Simulation, GlaxoSmithKline R&D, Brentford, UK.ORCID 0000-0002-6211-1430
Annette S GrossClinical Pharmacology Modelling and Simulation, GlaxoSmithKline R&D, Ermington, Australia.ORCID 0000-0001-9567-0127
GlaxoSmithKline (Australia) · AUGlaxoSmithKline (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Treatment response to clopidogrel is associated with CYP2C19 activity through the formation of the active H4 metabolite. The aims of this study were to develop a physiologically based pharmacokinetic (PBPK) model of clopidogrel and its metabolites for populations of European ancestry, to predict the pharmacokinetics in the Japanese population by CYP2C19 phenotype, and to investigate the effect of clinical and demographic factors. A PBPK model was developed and verified to describe the two metabolic pathways of clopidogrel (H4 metabolite, acyl glucuronide metabolite) for a population of European ancestry using plasma data from published studies. Subsequently, model predictions in the Japanese population were evaluated. The effects of CYP2C19 activity, fluvoxamine coadministration (CYP2C19 inhibitor), and population-specific factors (age, sex, BMI, body weight, cancer, hepatic, and renal dysfunction) on the pharmacokinetics of clopidogrel and its metabolites were then characterized. The predicted/observed ratios for clopidogrel and metabolite exposure parameters were acceptable (twofold acceptance criteria). For all CYP2C19 phenotypes, steady-state AUC

Indexed as

GlucuronidesKidney DiseasesClopidogrelCytochrome P-450 CYP2C19FemaleFluvoxamineHumansJapanMaleClopidogrelCYP2C19 protein, humanCytochrome P-450 CYP2C19FluvoxamineGlucuronidesclopidogrelCYP2C19inter-ethnic differencesmetabolitesPBPK modelling

Identifiers

PMID35307978
PMCPMC8934724
OpenAlexW4220684773

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.