Trial reportJournal of clinical pharmacology2014
Effectiveness of clopidogrel dose escalation to normalize active metabolite exposure and antiplatelet effects in CYP2C19 poor metabolizers.
Trial report in Journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01341600 (Clopidogrel Pharmacogenetics Bench to Bedside - A Practical Application), which is not on this map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clopidogrel Pharmacogenetics Bench to Bedside - A Practical Application
Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Clopidogrel in Critically Ill Patients.Clinical pharmacology and therapeutics · 2018Trial
- UGT1A1 genotype-dependent dose adjustment of belinostat in patients with advanced cancers using population pharmacokinetic modeling and simulation.Journal of clinical pharmacology · 2016Trial
- Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2016Trial
- The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.Current vascular pharmacology · 2016Trial
- Genetic Determinants of Response to P2YInterventional cardiology clinics · 2024Review
- Review
- Article
- The influence of acute coronary syndrome on levels of clopidogrel active metabolite and platelet inhibition in patients with and without CYP2C19*2(681 G>A), *3(636 G>A) and ABCB1(C3435C> T) gene polymorphisms.Postepy w kardiologii interwencyjnej = Advances in interventional cardiology · 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
- Clinical application and importance of one-step human CYP2C19 genotype detection.The Journal of international medical research · 2018Article
- Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling HNature communications · 2018Article
- Article
- Role of genetic testing in patients undergoing percutaneous coronary intervention.Expert review of clinical pharmacology · 2018Review
- Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite.European journal of clinical pharmacology · 2017Article
- Genetic Determinants of P2YInterventional cardiology clinics · 2017Review
- Clinically relevant genetic variants of drug-metabolizing enzyme and transporter genes detected in Thai children and adolescents with autism spectrum disorder.Neuropsychiatric disease and treatment · 2016Article
- Clinical pharmacokinetics and pharmacodynamics of clopidogrel.Clinical pharmacokinetics · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Carriers of two copies of the loss-of-function CYP2C19*2 variant convert less clopidogrel into its active metabolite, resulting in diminished antiplatelet responses and higher cardiovascular event rates. To evaluate whether increasing the daily clopidogrel dose in poor metabolizers (PM) overcomes the effect of the CYP2C19 * 2 variant, we enrolled 18 healthy participants in a genotype-stratified, multi-dose, three-period, fixed-sequence crossover study. Six participants with the *1/*1 extensive (EM), *1/*2 intermediate (IM), and *2/*2 poor metabolizer genotypes each received 75 mg, 150 mg, and 300 mg each for 8 days. In each period, maximal platelet aggregation 4 hours post-dose (MPA4) and active metabolite area under the curve (AUC) differed among genotype groups (P < .05 for all). At day 8, PMs needed 300 mg daily and IMs needed 150 mg daily to attain a similar MPA4 as EMs on the 75 mg dose (32.6%, 33.2%, 31.3%, respectively). Similarly, PMs needed 300 mg daily to achieve active metabolite concentrations that were similar to EMs on 75 mg (AUC 37.7 and 33.5 ng h/mL, respectively). These results suggest that quadrupling the usual clopidogrel dose might be necessary to overcome the effect of poor CYP2C19 metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.