Related Experiment Video
Updated: Jun 19, 2026
08:46
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Clopidogrel resistance: fact and fiction
J W van Werkum1, A A C M Heestermans, V H M Deneer
1Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
Future Cardiology
|October 7, 2009
Summary
Clopidogrel with aspirin reduces thrombotic events, but response varies greatly. Understanding factors like absorption and drug interactions is key to managing clopidogrel resistance.
Area of Science:
- Pharmacology
- Cardiology
- Thrombosis Research
Background:
- Clopidogrel and aspirin combination therapy is vital for preventing thrombotic events in acute coronary syndromes and after percutaneous coronary intervention.
- Significant interindividual variability in patient response to clopidogrel necessitates further investigation.
Purpose of the Study:
- To explore the factors contributing to variable patient responses to clopidogrel.
- To highlight the clinical relevance and prevalence of inadequate clopidogrel response.
- To recommend future research directions for assessing clopidogrel resistance.
Main Methods:
- Review of existing literature on clopidogrel response variability.
- Identification of factors influencing clopidogrel efficacy, including dosing, absorption, drug metabolism (CYP450 3A4/5), drug interactions, and genetic polymorphisms.
- Discussion of various platelet function assays used to measure clopidogrel response.
Main Results:
- Inadequate clopidogrel response rates vary widely based on measurement methods and definitions.
- Factors such as dosing, intestinal absorption, CYP450 activity, drug-drug interactions, and genetic variations impact clopidogrel response.
- Clinical relevance of inadequate clopidogrel response has been demonstrated in recent studies.
Conclusions:
- Accurate assessment of clopidogrel resistance requires standardized, sensitive assays focusing on P2Y12 receptor inhibition.
- Future research should utilize rapid, simple tests like vasodilator-stimulated phosphoprotein (VASP) assay or platelet aggregate stabilization measurements.
- Understanding and addressing clopidogrel resistance is crucial for optimizing antiplatelet therapy outcomes.
Related Concept Videos
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
02:56Treatment Resistant Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
01:25Clinical Significance of Antibiotic Resistance
Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:27Pharmacogenetics of Drug Metabolism: Overview
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...