Artemisinins and Pyronaridine Phosphate Combination

Chang, Chen

doi:10.1016/b978-0-12-813133-6.00009-3

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…Today, the association of PYR and artesunate is among the most efficient and low-cost combination therapies for the treatment of malaria. [19] For about 20 years, PYR has been used to treat patients with uncomplicated malaria, with little knowledge about its mode of action.…”

Section: Introductionmentioning

confidence: 99%

Pyronaridine: An update of its pharmacological activities and mechanisms of action

Bailly

2020

Biopolymers

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Pyronaridine (PYR) is an erythrocytic schizonticide with a potent antimalarial activity against multidrug-resistant Plasmodium. The drug is used in combination with artesunate for the treatment of uncomplicated P. falciparum malaria, in adults and children. The present review briefly retraces the discovery of PYR and recent antimalarial studies which has led to the approval of PYR/artesunate combination (Pyramax) by the European Medicines Agency to treat uncomplicated malaria worldwide. PYR Pyronaridine (PYR, Figure 1), initially known as "antimalaria drug 7351", is a benzo-naphthyridine derivative originally synthesized in 1979 [1] and developed in China from the early 1980s. [2][3][4] Rapidly, experimental studies demonstrated that this compound was more active than chloroquine against different isolates of Plasmodium falciparum, the malaria pathogen.

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Section: Introductionmentioning

confidence: 99%

Pyronaridine: An update of its pharmacological activities and mechanisms of action

Bailly

2020

Biopolymers

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Preclinical Antimalarial Combination Study of M5717, a Plasmodium falciparum Elongation Factor 2 Inhibitor, and Pyronaridine, a Hemozoin Formation Inhibitor

Rottmann

Jonat

Dhingra

et al. 2020

Antimicrob Agents Chemother

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Antimalarial drug resistance in the Plasmodium falciparum parasite poses a constant challenge for drug development. To mitigate this risk, new antimalarial medicines should be developed as fixed-dose combinations. Assessing the pharmacodynamic interactions of potential antimalarial drug combination partners during early phases of development is essential in developing the targeted parasitological and clinical profile of the final drug product. Here, we have studied the combination of M5717, a P. falciparum translation elongation factor 2 inhibitor, and pyronaridine, an inhibitor of hemozoin formation. Our test cascade consisted of in vitro isobolograms as well as in vivo studies in the P. falciparum severe combined immunodeficient (SCID) mouse model. We also analyzed pharmacokinetic and pharmacodynamic parameters, including genomic sequencing of recrudescent parasites. We observed no pharmacokinetic interactions with the combination of M5717 and pyronaridine. M5717 did not negatively impact the rate of kill of the faster-acting pyronaridine, and the latter was able to suppress the selection of M5717-resistant mutants, as well as significantly delay the recrudescence of parasites both with suboptimal and optimal dosing regimens.

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Artemisinins and Pyronaridine Phosphate Combination

Cited by 2 publications

References 16 publications

Pyronaridine: An update of its pharmacological activities and mechanisms of action

Pyronaridine: An update of its pharmacological activities and mechanisms of action

Preclinical Antimalarial Combination Study of M5717, a Plasmodium falciparum Elongation Factor 2 Inhibitor, and Pyronaridine, a Hemozoin Formation Inhibitor

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