Investigation of Drug-drug Interaction Between Clopidogrel and Fluoxetine (PLATINE)

Centre Hospitalier Universitaire de Saint Etienne

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Fluoxetine+clopidogrel then clopidogrel; Drug: Clopidogrel then fluoxetine+clopidogrel

Study type: Interventional

Funder types: Other

Identifiers

NCT00732290

0801068

2008-004395-46

Details and patient eligibility

About

Clopidogrel is a platelet aggregation inhibitor witch prevents thrombotic events in patients with atherosclerotic vascular disease. To date, 4 to 30 % of patients are considered as poor, low or non-responder to this therapeutic. However, drug-drug interactions may lead to decrease the clopidogrel responsiveness. Many arguments are in support to a drug-drug interaction between clopidogrel and fluoxetine (selective serotonin reuptake inhibitor). On the pharmacokinetic level, fluoxetine inhibits the cytochroms involved in the production of clopidogrel active metabolite. On the pharmacodynamic level fluoxetine could increase the risk of hemorrhage by inhibiting the serotonin platelet reuptake and thus enhance the antiplatelet effect of clopidogrel.

The purpose of this study is to investigate the influence of fluoxetine on pharmacokinetic and pharmacodynamic of clopidogrel.

Enrollment: 10 patients

Sex: Male

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Signed an informed consent
• Body mass: 60 to 85 Kg
• Platelet count: 180 to 350 G/L
• % platelet aggregation > 70%
• Subjects are to be in good health as determined by a medical history, physical examination including vital signs, and clinical laboratory test results including liver function, renal and full blood count

Exclusion criteria

• Subject with an history of seizure disorder
• Subject with a known allergy fluoxetine or clopidogrel
• Cigarette smoking
• Subject with a history of hemorrhagic disease
• Peptic ulcer
• Psychiatric disorders
• Participation in another clinical or device trial within the three previous months
• Subject who is currently taking medications
• Subject who is currently taking medications for depression
• Subject with an history of depression (MADRS score < 15)
• Hepatic insufficiency

Trial design

10 participants in 2 patient groups

1

Active Comparator group

Description:

Clopidogrel then fluoxetine+clopidogrel

Treatment:

Drug: Clopidogrel then fluoxetine+clopidogrel

2

Active Comparator group

Description:

Fluoxetine+clopidogrel then clopidogrel

Treatment:

Drug: Fluoxetine+clopidogrel then clopidogrel