ArticleEuropean journal of clinical pharmacology2017
Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite.
Article in European journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- Influence of Genetic and Epigenetic Factors of P2YCardiovascular drugs and therapy · 2024Review
- Integrating Clopidogrel's First-Pass Effect in a Joint Semi-Physiological Population Pharmacokinetic Model of the Drug and Its Inactive Carboxylic Acid Metabolite.Pharmaceutics · 2024Article
- IsGenes · 2024Article
- Population pharmacokinetic-pharmacodynamic modeling of clopidogrel for dose regimen optimization based on CYP2C19 phenotypes: A proof of concept study.CPT: pharmacometrics & systems pharmacology · 2024Article
- Article
- Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.Clinical pharmacology and therapeutics · 2021Article
- The Dynamic Effect of Non-CYP3A4-Metabolized and CYP3A4-Metabolized Statins on Clopidogrel Resistance in Patients With Cerebral Infarction.Frontiers in pharmacology · 2021Article
- Pharmacokinetics and Pharmacodynamics of Approved and Investigational P2Y12 Receptor Antagonists.Clinical pharmacokinetics · 2020Review
- Physiologically-Based Pharmacokinetic-Pharmacodynamics Model Characterizing CYP2C19 Polymorphisms to Predict Clopidogrel Pharmacokinetics and Its Anti-Platelet Aggregation Effect Following Oral Administration to Coronary Artery Disease Patients With or Without Diabetes.Frontiers in pharmacology · 2020Article
- Differing Membrane Interactions of Two Highly Similar Drug-Metabolizing Cytochrome P450 Isoforms: CYP 2C9 and CYP 2C19.International journal of molecular sciences · 2019Article
- Effects of different CYP2C19 genotypes on prognosis of patients complicated with atrial fibrillation taking clopidogrel after PCI.Experimental and therapeutic medicine · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
purposeA high interindividual variability is observed in the pharmacokinetics of clopidogrel, a widely used antiplatelet drug. In the present study, a joint parent-metabolite population pharmacokinetic model was developed to adequately describe observed concentrations of clopidogrel and its active thiol metabolite (H4).
methodsThe study included 63 patients undergoing elective coronarography or percutaneous coronary intervention. The population pharmacokinetic model was developed in the NONMEM 7.3 software, and first-order conditional estimation method with interaction was applied. Also, the influence of covariates was evaluated (age, weight, body mass index (BMI), obesity defined as BMI ≥ 30 kg/m
resultsIt was found that the only significant covariate was the presence of CYP2C19*2 allele, which had an impact on lower conversion of clopidogrel to H4. As a result, predicted area under the time-concentration curve values was lower in carriers of this allele, with median 5.94 ng h/ml (interquartile range 3.92-12.51 [ng∙h/ml]) vs. 12.70 ng h/ml in non-carriers (interquartile range, 7.00-19.39 [ng∙h/ml]), respectively (p = 0.004).
conclusionsDeveloped model predicts that the only significant covariate influencing the observed concentrations and therefore the exposure to the active H4 metabolite is the presence of CYP2C19*2 allele.
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