Related Experiment Video

Updated: Jun 25, 2026

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
07:00

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene

Published on: April 1, 2019

Clopidogrel resistance: pharmacokinetic or pharmacogenetic?

Neville F Ford1

  • 1Woodfield Clinical Consulting LLC, Green Valley, AZ 85622, USA. neville@woodfieldclinical.com

Journal of Clinical Pharmacology
|February 28, 2009
PubMed

Insights

Clopidogrel resistance, a reduced platelet response to the drug, is linked to a patient's intrinsic platelet properties and genetic variations in the CYP2C19 gene. This genetic factor influences how effectively clopidogrel works, particularly in patients with acute coronary syndromes.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Platelet Biology

Background:

  • Clopidogrel, combined with aspirin, is a standard treatment for acute coronary syndromes and post-coronary stent placement.
  • Clopidogrel resistance, characterized by inadequate platelet aggregation response, has been observed in clinical practice.
  • This resistance can compromise treatment efficacy, necessitating further investigation into its underlying mechanisms.

Purpose of the Study:

  • To investigate the phenomenon of clopidogrel resistance.
  • To identify the intrinsic factors contributing to clopidogrel resistance.
  • To explore the genetic basis and potential mechanisms of clopidogrel resistance.

Main Methods:

  • Analysis of patient platelet aggregation responses to adenosine diphosphate challenges.
  • Investigation of the EXCELSIOR study data to understand resistance onset.
  • Examination of genetic polymorphisms, specifically in the CYP2C19 gene, associated with clopidogrel resistance.

Main Results:

  • Clopidogrel resistance is an intrinsic patient platelet property, present before treatment.
  • A defective CYP2C19 gene allele (*2) is associated with clopidogrel resistance.
  • A dose-response relationship exists, with CYP2C19*2/*2 homozygotes showing poorer response than heterozygotes and wild-type homozygotes.

Conclusions:

  • CYP2C19 genotype significantly impacts clopidogrel efficacy.
  • While CYP3A4 is the major metabolic pathway, CYP2C19 polymorphisms play a crucial role.
  • A potential linkage between P2Y12 receptor polymorphism and CYP2C19 polymorphism warrants further study.

Related Concept Videos

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic 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...
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics 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...
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: 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...