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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 10/2018

01-10-2018 | Original Research Article

Impact of Boosted Antiretroviral Therapy on the Pharmacokinetics and Efficacy of Clopidogrel and Prasugrel Active Metabolites

Authors: Niloufar Marsousi, Youssef Daali, Pierre Fontana, Jean-Luc Reny, Virginie Ancrenaz-Sirot, Alexandra Calmy, Serge Rudaz, Jules Alexandre Desmeules, Caroline Flora Samer

Published in: Clinical Pharmacokinetics | Issue 10/2018

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Abstract

Background and objectives

Prasugrel and clopidogrel are inhibitors of the ADP-P2Y12 platelet receptor used in acute coronary syndrome patients. They require bioactivation via isoenzymes such as cytochrome P450 (CYP) 3A4, CYP2C19 and CYP2B6. Ritonavir and cobicistat are potent CYP3A inhibitors, prescribed as pharmacokinetic (PK) enhancers in the treatment of human immunodeficiency virus (HIV) infection.

Methods

In this study, the impact of boosted antiretroviral therapies (ARTs) on the PK of clopidogrel and prasugrel active metabolites (AMs), and on the efficacy of prasugrel and clopidogrel, were evaluated in a randomized crossover clinical trial.

Results

A significantly lower exposure to clopidogrel AM [3.2-fold lower area under the concentration–time curve (AUC) and maximum plasma concentration (Cmax)] and prasugrel AM (2.1-fold and 1.7-fold lower AUC and Cmax) were demonstrated in HIV-infected patients treated with boosted ARTs compared with healthy controls; however, a differential impact was observed on platelet inhibition between clopidogrel and prasugrel. Clopidogrel 300 mg induced adequate (although modest) platelet inhibition in all healthy subjects, while platelet inhibition was insufficient in 44% of HIV patients. On the contrary, prasugrel 60 mg induced a potent platelet inhibition in both healthy and HIV-infected subjects.

Conclusion

Prasugrel appears to remain an adequate antiplatelet agent in HIV-infected patients and could be preferred to clopidogrel in this context, regardless of the metabolic interaction and inhibition of its bioactivation pathways.
Appendix
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Metadata
Title
Impact of Boosted Antiretroviral Therapy on the Pharmacokinetics and Efficacy of Clopidogrel and Prasugrel Active Metabolites
Authors
Niloufar Marsousi
Youssef Daali
Pierre Fontana
Jean-Luc Reny
Virginie Ancrenaz-Sirot
Alexandra Calmy
Serge Rudaz
Jules Alexandre Desmeules
Caroline Flora Samer
Publication date
01-10-2018
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 10/2018
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-018-0637-6

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