Drug intelligence / Profile preview

ritonavir + pyronaridine + artesunate

Development stage
Unknown
Lead developer
Medicines for Malaria Venture
Modality
Small Molecules
Administration
Oral
01

Overview

This is a combination of three drugs: ritonavir, pyronaridine, and artesunate. Ritonavir is an HIV protease inhibitor commonly used as a pharmacokinetic booster in antiretroviral therapy. Pyronaridine and artesunate are combined as an artemisinin-based antimalarial therapy (marketed as Pyramax), with pyronaridine acting as a Mannich base with potent antimalarial activity and artesunate being an artemisinin derivative that generates free radicals to inhibit *Plasmodium* parasites. The combination has been studied for drug-drug interactions, particularly because ritonavir can alter the metabolism of both pyronaridine and artesunate via effects on cytochrome P450 enzymes such as CYP3A4 and CYP2D6. In clinical studies, coadministration increased exposure to artesunate while decreasing its active metabolite dihydroartemisinin (DHA) levels; it also increased exposure to ritonavir itself[1][2][4][5]. The primary indication for the fixed-dose combination of pyronaridine/artesunate is malaria; ritonavir is primarily indicated for HIV infection.

02

Targets

GST (Glutathione S-transferase alpha 3)CYP2D6 (Cytochrome P450 2D6)PfATP6 (Plasmodium falciparum ATP6)CYP3A4 (Cytochrome P450 3A4)PR (Progesterone receptor)

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