Evidence map›Paper›PMID 38056237›Full record

ArticleBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2024

New insights into the role of VKORC1 polymorphisms for optimal warfarin dose selection in Caribbean Hispanic patients through an external validation of a population PK/PD model.

Karine Rodríguez-Fernández, Gledys Reynaldo-Fernández, Stephanie Reyes-González, Camila de Las Barreras, Leyanis Rodríguez-Vera, Cornelis Vlaar, Jean-Christophe M Monbaliu, Torsten Stelzer, Jorge Duconge, Victor Mangas-Sanjuan

Abstract read
In one paragraph

Article in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
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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

10 authors.

Karine Rodríguez-FernándezDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia, Spain.
Gledys Reynaldo-FernándezInstitute of Pharmacy and Foods, University of Havana, Havana 11300, Cuba.
Stephanie Reyes-GonzálezDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico - Medical Sciences Campus, San Juan 00936, PR, USA.
Camila de Las BarrerasInstitute of Pharmacy and Foods, University of Havana, Havana 11300, Cuba.
Leyanis Rodríguez-VeraCenter for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA.
Cornelis VlaarDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico - Medical Sciences Campus, San Juan 00936, PR, USA.
Jean-Christophe M MonbaliuCenter for Integrated Technology and Organic Synthesis, MolSys Research Unit, University of Liège, B-4000 Liège (Sart Tilman), Liège, Belgium.
Torsten StelzerDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico - Medical Sciences Campus, San Juan 00936, PR, USA; Crystallization Design Institute, Molecular Sciences Research Center, University of Puerto Rico, San Juan 00926, PR, USA.
Jorge DucongeDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico - Medical Sciences Campus, San Juan 00936, PR, USA. Electronic address: jorge.duconge@upr.edu.
Victor Mangas-SanjuanDepartment of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia, Spain; Interuniversity Research Institute for Molecular Recognition and Technological Development, Polytechnic University of Valencia-University of Valencia, Valencia, Spain.

Funding

Merging artificial intelligence (AI) and pharmacometrics to elucidate gene-drug interactions linked to clopidogrel responsiveness in genetically heterogeneous patientsR16GM149372 · NIGMS · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI Jorge Duconge · 2023 to 2026
$596k
NIGMS NIH HHS R16 GM149372
6 · The paper itself

Abstract

Warfarin, an oral anticoagulant, has been used for decades to prevent thromboembolic events. The complex interplay between CYP2C9 and VKORC1 genotypes on warfarin PK and PD properties is not fully understood in special sub-groups of patients. This study aimed to externally validate a population pharmacokinetic/pharmacodynamic (PK/PD) model for the effect of warfarin on international normalized ratio (INR) and to evaluate optimal dosing strategies based on the selected covariates in Caribbean Hispanic patients. INR, and CYP2C9 and VKORC1 genotypes from 138 patients were used to develop a population PK/PD model in NONMEM. The structural definition of a previously published PD model for INR was implemented. A numerical evaluation of the parameter-covariate relationship was performed. Simulations were conducted to determine optimal dosing strategies for each genotype combinations, focusing on achieving therapeutic INR levels. Findings revealed elevated IC

Indexed as

Aryl Hydrocarbon HydroxylasesWarfarinAnticoagulantsCaribbean PeopleCytochrome P-450 CYP2C9GenotypeHispanic or LatinoHumansVitamin K Epoxide ReductasesAnticoagulantsAryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2C9Vitamin K Epoxide ReductasesVKORC1 protein, humanWarfarinCYP2C9Hispanic CaribbeanPharmacokinetic/pharmacodynamicVKORC1Warfarin

Identifiers

PMID38056237
PMCPMC10853672

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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.