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Preparation of Washed Human Platelets for Quantitative Metabolic Flux Studies
Published on: January 10, 2025
The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and
Arwa M Amin1, Lim Sheau Chin1, Dzul Azri Mohamed Noor1
1School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
Insights
Clopidogrel therapy response varies significantly, impacting cardiovascular event outcomes. Pharmacometabolomics offers a promising approach to personalize clopidogrel treatment by identifying novel biomarkers and metabolic pathways.
Area of Science:
- Cardiovascular pharmacology
- Personalized medicine
- Metabolomics
Background:
- Dual antiplatelet therapy with aspirin and clopidogrel is crucial after percutaneous coronary intervention.
- Variable platelet reactivity to clopidogrel can lead to treatment failure and cardiovascular events.
- Current personalization methods for clopidogrel therapy show limitations in precise outcome prediction.
Purpose of the Study:
- To review factors influencing variable platelet reactivity to clopidogrel.
- To appraise current clopidogrel personalization strategies.
- To explore the potential of pharmacometabolomics in predicting clopidogrel response and outcomes.
Main Methods:
- Literature review of factors affecting clopidogrel response.
- Evaluation of existing clopidogrel personalization methods (e.g., CYP2C19 genotyping, pharmacokinetics, platelet function testing).
- Review of pharmacometabolomics applications in predicting drug response and its potential for clopidogrel.
Main Results:
- Numerous genetic and non-genetic factors contribute to variable clopidogrel response, with many remaining unexplained.
- Current personalization methods provide insufficient prediction accuracy for clopidogrel outcomes.
- Pharmacometabolomics identifies novel biomarkers and metabolic pathways related to drug response, offering deeper insights than traditional methods.
Conclusions:
- Personalizing clopidogrel therapy remains challenging due to unexplained variability in platelet reactivity.
- Integrating pharmacogenetics with pharmacometabolomics may elucidate unknown factors influencing clopidogrel response.
- Pharmacometabolomics holds significant promise for improving the prediction of clopidogrel outcomes and enabling personalized treatment strategies.
Abstract:
Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response. This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome.
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