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To test pharmacodynamic response to clopidogrel 150mg once daily during 7 days in healthy subjects carriers of a mutated allele (*2) associated with CYP2C19 deficiency and non responders to the usual regimen of 75 mg once daily
Thirty individuals genotyped for specific variants of 2C19 cytochrome and P2Y12 platelet ADP receptor will receive during one week a daily dose of 75 mg of clopidogrel. Depending on their pharmacodynamic response to this dose of clopidogrel, subjects will be affiliated to two groups, "good responders" and "bad responders". After a wash-out period, "bad responders" will receive a double dose of clopidogrel, while the "good responders" will receive 75 mg of clopidogrel, associated with a CYP2C19 inhibitor. Such study will allow to evaluate both the impact of raising daily dose of clopidogrel in patients with defected variants of 2C19 and potential interactions of clopidogrel with other drugs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Clopidogrel |
|
| 2 | Experimental | Clopidogrel |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clopidogrel | Drug | Clopidogrel |
|
| Measure | Description | Time Frame |
|---|---|---|
| Inhibition platelet activity index (ADP induced aggregation) measured between | during 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Clopidogrel and metabolites pharmacokinetics and relation to dynamics | during 7 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean Sébastien HULOT, MD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Européen Georges Pompidou | Paris | 75015 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16772608 | Result | Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, Aiach M, Lechat P, Gaussem P. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006 Oct 1;108(7):2244-7. doi: 10.1182/blood-2006-04-013052. Epub 2006 Jun 13. |
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| ID | Term |
|---|---|
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
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| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |