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A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy

Warfarin is the current standard of care in oral anticoagulation therapy. It is commonly prescribed to treat venous thromboembolism, pulmonary embolism, acute myocardial infarction, and to decrease the risk of stroke in atrial fibrillation. Warfarin therapy is challenging because of marked and often...

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Autor principal: Bosch, Luis Ángel Bermúdez
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181534/
https://www.ncbi.nlm.nih.gov/pubmed/25285240
http://dx.doi.org/10.4172/2153-0645.T-001
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author Bosch, Luis Ángel Bermúdez
author_facet Bosch, Luis Ángel Bermúdez
author_sort Bosch, Luis Ángel Bermúdez
collection PubMed
description Warfarin is the current standard of care in oral anticoagulation therapy. It is commonly prescribed to treat venous thromboembolism, pulmonary embolism, acute myocardial infarction, and to decrease the risk of stroke in atrial fibrillation. Warfarin therapy is challenging because of marked and often unpredictable inter-individual dosing variations that effectively reach and maintain adequate anticoagulation. Several researchers have developed pharmacogenetic-guided maintenance dose algorithms that incorporate genetics and individual patient characteristics. However, there is limited information available concerning dosing during warfarin initiation. This is considered the most clinically challenging therapeutic phase. In such, the risk of recurrent thromboembolism and hemorrhage are elevated. The objective of this retrospective study is to predict the individual initial doses for Puerto Rican patients (n=175) commencing anticoagulation therapy at Veterans Affairs Caribbean Healthcare System (VACHS) using pharmacogenetic/pharmacokinetic-driven model. A pharmacogenetic driven model (R2=0.4809) was developed in Puerto Rican patients and combined with pharmacokinetic formulas that enabled us to predict the individual initial doses for patients (n=121) commencing anticoagulation therapy. WinNonlin® pharmacokinetic-pharmacodynamic simulations were carried out to determine the predictability of this model. This model demonstrated promising results with few (n=10) simulations outside of their respective therapy range. A customized pharmacogenetic-based warfarin maintenance dose algorithm (R2=0.7659) was developed in a derivation cohort of 131 patients. The predictability of this developed pharmacogenetic algorithm was compared with the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm and it demonstrated superior predictability within our study population.
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spelling pubmed-41815342014-10-02 A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy Bosch, Luis Ángel Bermúdez J Pharmacogenomics Pharmacoproteomics Article Warfarin is the current standard of care in oral anticoagulation therapy. It is commonly prescribed to treat venous thromboembolism, pulmonary embolism, acute myocardial infarction, and to decrease the risk of stroke in atrial fibrillation. Warfarin therapy is challenging because of marked and often unpredictable inter-individual dosing variations that effectively reach and maintain adequate anticoagulation. Several researchers have developed pharmacogenetic-guided maintenance dose algorithms that incorporate genetics and individual patient characteristics. However, there is limited information available concerning dosing during warfarin initiation. This is considered the most clinically challenging therapeutic phase. In such, the risk of recurrent thromboembolism and hemorrhage are elevated. The objective of this retrospective study is to predict the individual initial doses for Puerto Rican patients (n=175) commencing anticoagulation therapy at Veterans Affairs Caribbean Healthcare System (VACHS) using pharmacogenetic/pharmacokinetic-driven model. A pharmacogenetic driven model (R2=0.4809) was developed in Puerto Rican patients and combined with pharmacokinetic formulas that enabled us to predict the individual initial doses for patients (n=121) commencing anticoagulation therapy. WinNonlin® pharmacokinetic-pharmacodynamic simulations were carried out to determine the predictability of this model. This model demonstrated promising results with few (n=10) simulations outside of their respective therapy range. A customized pharmacogenetic-based warfarin maintenance dose algorithm (R2=0.7659) was developed in a derivation cohort of 131 patients. The predictability of this developed pharmacogenetic algorithm was compared with the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm and it demonstrated superior predictability within our study population. 2014-01-25 /pmc/articles/PMC4181534/ /pubmed/25285240 http://dx.doi.org/10.4172/2153-0645.T-001 Text en © 2014 Bermudez-Bosch LA. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Article
Bosch, Luis Ángel Bermúdez
A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy
title A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy
title_full A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy
title_fullStr A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy
title_full_unstemmed A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy
title_short A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy
title_sort proposal for an individualized pharmacogenetic-guided warfarin dosage regimen for puerto rican patients commencing anticoagulation therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181534/
https://www.ncbi.nlm.nih.gov/pubmed/25285240
http://dx.doi.org/10.4172/2153-0645.T-001
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