Trial reportJournal of pharmacokinetics and pharmacodynamics2008
Population pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in aspirin-treated patients with stable coronary artery disease.
Trial report in Journal of pharmacokinetics and pharmacodynamics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Population Pharmacokinetic/Pharmacodynamic Models for P2Y12 Inhibitors: A Systematic Review and Clinical Appraisal Using Exposure Simulation.Clinical pharmacokinetics · 2024Pooled it
- Population Pharmacokinetic and Exposure-Response Analyses of Prasugrel in Pediatric Patients with Sickle Cell Anemia.Clinical pharmacokinetics · 2018Trial
- Platelet Aggregation Inhibitory Effects and Pharmacokinetics of Prasugrel Used in Combination With Aspirin in Healthy Japanese Subjects.Clinical pharmacology in drug development · 2017Trial
- 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
- Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients.Journal of thrombosis and thrombolysis · 2014Trial
- Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects.Acta pharmacologica Sinica · 2012Trial
- The pharmacokinetics and pharmacodynamics of prasugrel in healthy Chinese, Japanese, and Korean subjects compared with healthy Caucasian subjects.European journal of clinical pharmacology · 2010Trial
- 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
- Mind the Gap: Model-Based Switching from Selatogrel to Maintenance Therapy with Oral P2Y12 Receptor Antagonists.Biomolecules · 2023Article
- Pharmacogenetics of Antiplatelet Therapy.Annual review of pharmacology and toxicology · 2023Review
- Pharmacokinetic/pharmacodynamic modeling of drug interactions at the P2YCPT: pharmacometrics & systems pharmacology · 2021Article
- Pharmacokinetics and Pharmacodynamics of Approved and Investigational P2Y12 Receptor Antagonists.Clinical pharmacokinetics · 2020Review
- Clopidogrel Pharmacogenetics.Circulation. Cardiovascular interventions · 2019Review
- The association of clopidogrel and 2-oxo-clopidogrel plasma levels and the 40 months clinical outcome after primary PCI.International journal of clinical pharmacy · 2018Article
- Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite.European journal of clinical pharmacology · 2017Article
- Pharmacology of antiplatelet agents.Current atherosclerosis reports · 2013Review
- Review
- Evolving role of platelet function testing in coronary artery interventions.Vascular health and risk management · 2012Review
- Genotypic and phenotypic assessment of platelet function and response to P2Y12 antagonists.Current cardiology reports · 2011Review
- Effect of intrinsic and extrinsic factors on the clinical pharmacokinetics and pharmacodynamics of prasugrel.Clinical pharmacokinetics · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of the current analysis was to characterize the population PK of prasugrel and clopidogrel metabolites, the resulting PD response, and identification of covariates for key PK/PD parameters. Aspirin-treated subjects with coronary artery disease were randomized to double-blind treatment with clopidogrel 600 mg loading dose (LD) followed by daily 75 mg maintenance dose (MD) or prasugrel 60 mg LD and daily 10 mg MD for 28 days. Plasma concentrations of prasugrel active metabolite (Pras-AM) and prasugrel's inactive thiolactone metabolite (Pras-thiolactone) were simultaneously fit to a multicompartmental model; a similar model adequately described clopidogrel's active metabolite (Clop-AM) PK. By linking to the PK model through the active metabolite concentrations, the PK/PD model characterized the irreversible inhibition of platelet aggregation through a sigmoidal Emax model. Although dose, sex, and weight were identified as significant covariates in the prasugrel PK model, only the effect of body weight produced significant changes in Pras-AM exposure. Generally, these factors resulted in only minor changes in Pras-AM exposures such that, overall, the change in the resulting maximal platelet aggregation (MPA) was predicted to be < or =10% points on average. The clopidogrel PK model included dose as a covariate indicating that a significantly less-than-proportional increase in Clop-AM exposure is expected over the dose range of 75-600 mg, thus, the model-predicted PD response is lower than might be anticipated given an 8-fold difference in dose and lower than that typically achieved following prasugrel 60 mg LD. The greater PD response with prasugrel compared with clopidogrel was accounted for by greater conversion of dose to active metabolite.
Indexed as
Identifiers
19023649What OpenQuestion holds
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.