Trial reportBritish journal of clinical pharmacology2016
The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes.
Trial report in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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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.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- Effects of CYP2C19 and CYP3A5 genetic polymorphisms on the pharmacokinetics of cilostazol and its active metabolites.European journal of clinical pharmacology · 2018Trial
- The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes.British journal of clinical pharmacology · 2016Trial
- Review
- The polygenic implication of clopidogrel responsiveness: Insights from platelet reactivity analysis and next-generation sequencing.PloS one · 2024Article
- Article
- Drug-Drug-Gene Interactions in Cardiovascular Medicine.Pharmacogenomics and personalized medicine · 2022Review
- 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
- Association between CYP2C19 genotype and the additional effect of cilostazol to clopidogrel resistance in neuroendovascular therapy.Nagoya journal of medical science · 2018Article
- Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy.Drug metabolism and personalized therapy · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe primary objective of the present study was to evaluate the pharmacokinetic and pharmacodynamic interactions between clopidogrel and cilostazol in relation to the CYP2C19 and CYP3A5 genotypes.
methodsIn a randomized, three-way crossover study, 27 healthy subjects were administered clopidogrel (300 mg), cilostazol (100 mg) or clopidogrel + cilostazol orally. Plasma concentrations of clopidogrel, cilostazol and their active metabolites (clopidogrel thiol metabolite, 3,4-dehydrocilostazol and 4″-trans-hydroxycilostazol), and adenosine diphosphate-induced platelet aggregation were measured for pharmacokinetic and pharmacodynamic assessment.
resultsThe area under the plasma concentration-time curve (AUC) of the active thiol metabolite of clopidogrel was highest in the CYP2C19 extensive metabolizers (EM) and lowest in the poor metabolizers (PM). Cilostazol decreased the thiol metabolite AUC by 29% in the CYP3A5*1/*3 genotype [geometric mean ratio (GMR) 0.71; 90% confidence interval (CI) 0.58, 0.86; P = 0.020] but not in the CYP3A5*3/*3 genotype (GMR 0.93; 90% CI 0.80, 1.10; P = 0.446). Known effects of the CYP2C19 and CYP3A5 genotypes on the exposure of cilostazol and its metabolites were observed but there was no significant difference in the AUC of cilostazol and 3,4-dehydrocilostazol between cilostazol and clopidogrel + cilostazol. The inhibition of platelet aggregation from 4 h to 24 h (IPA4-24 ) following the administration of clopidogrel alone was highest in the CYP2C19 EM genotype and lowest in the CYP2C19 PM genotype (59.05 ± 18.95 vs. 36.74 ± 13.26, P = 0.023). However, the IPA of the CYP2C19 PM following co-administration of clopidogrel and cilostazol was comparable with that of the CYP2C19 EM and intermediate metabolizers (IM) only in CYP3A5*3/*3 subjects.
conclusionsThe additive antiplatelet effect of cilostazol plus clopidogrel is maximized in subjects with both the CYP2C19 PM and CYP3A5*3/*3 genotypes because of a lack of change of clopidogrel thiol metabolite exposure in CYP3A5*3/*3 as well as the highest cilostazol IPA in CYP2C19 PM and CYP3A5*3/*3 subjects.
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Registered trials
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