Pharmacokinetic Interaction Between Ritonavir and Prasugrel in Healthy Volunteers
Status:
Completed
Trial end date:
2011-09-01
Target enrollment:
Participant gender:
Summary
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.