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HIV patients are at particular risk to develop cardiovascular disease (CVD) as they exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the non nucleosidic reverse transcriptase inhibitors (NNRTI) and/or protease inhibitors (PI) drug classes is associated with dyslipidemia known to increase the risk of coronary heart disease particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication. HIV patients could thus potentially receive anti-aggregant therapy concomitantly with their antiretroviral treatment. Prasugrel is an anti-aggregating agent indicated to prevent the recurrence of ischemic events after coronary arteries stenting. It is a pro-drug mainly metabolized by cytochromes P450 (CYP) 3A and 2B6 and to a lesser extent by CYP2C9 and 2C19. Ritonavir is an anti-protease and CYP3A4 and CYP2B6 inhibitor used in anti-HIV therapy. The aim of the present study is to assess the potential drug-drug interaction between prasugrel and the CYP3A/2B6 inhibitor ritonavir. Ten healthy volunteers will receive prasugrel 10mg alone or after 100mg ritonavir. The effect of ritonavir on prasugrel pharmacokinetics will be assessed. The two sessions will be separated by a one-week "wash out" period. During each session, CYP3A, 2B6, 2C9 and 2C19 activities will be assessed by a micrococktail approach with microdoses of midazolam, bupropion, flurbiprofen and omeprazole. The pharmacokinetics of prasugrel active metabolite will be assessed during the two sessions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prasugrel 10mg po | Experimental |
| |
| Prasugrel 10mg po + ritonavir 100mg po | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prasugrel | Drug | Assessment of prasugrel metabolic ratio and phenotyping of CYP2B6/2C9/2C19/3A4 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasmatic prasugrel metabolites concentrations (ng/mL) in presence/absence of ritonavir | The concentrations will be measured at 9 differents times during 6 hours (0,1min,30min,1H,1H30,2H,3H,4H,6H). The measurements will be repeated one week later for 6 hours | One week |
| Measure | Description | Time Frame |
|---|---|---|
| CYP2B6 phenotype in presence/absence of ritonavir | The phenotype will be assessed by taking a blood sample once and one week later | One week |
| CYP2C9 phenotype in presence/absence of ritonavir | The phenotype will be assessed by taking a blood sample once and one week later |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jules A Desmeules, Pr | University Hospital, Geneva | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals | Geneva | 1211 | Switzerland |
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| ID | Term |
|---|---|
| D000068799 | Prasugrel Hydrochloride |
| D019438 | Ritonavir |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D010879 | Piperazines |
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| Ritonavir | Drug | Assessment of prasugrel metabolic ratio and phenotyping of CYP2B6/2C9/2C19/3A4 in presence of ritonavir |
|
| one week |
| CYP2C19 phenotype in presence/absence of ritonavir | The phenotype will be assessed by taking a blood sample once and one week later | one week |
| CYP3A4 phenotype in presence/absence of ritonavir | The phenotype will be assessed by taking a blood sample once and one week later | one week |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013844 | Thiazoles |
| D001393 | Azoles |