In vitro and in vivo interaction of synthetic peroxide RBx11160 (OZ277) with piperaquine in Plasmodium models.
RBx11160 (OZ277) is a promising antimalarial drug candidate that Ranbaxy Laboratories Limited and Medicines for Malaria Venture (MMV) are currently developing as a fixed combination with piperaquine. Here, we describe the in vitro (Plasmodium falciparum) and in vivo (Plasmodium berghei) activities of piperaquine in combination with RBx11160 and artemether. In vitro, both combinations demonstrated a slight tendency towards antagonism with mean sums of fractional inhibitory concentrations (mean Sigma FICs) of 1.5. In vivo, piperaquine and artemether were borderline antagonistic (mean Sigma FIC of 1.4). However, an additive in vivo interaction of piperaquine and RBx11160 (mean Sigma FIC of 1.1) was identified, suggesting that a RBx11160-piperaquine combination therapy in humans should allow each molecule to exert its full antimalarial effect.
Snyder
Christopher
C
Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland.
Chollet
Jacques
J
Santo-Tomas
Josefina
J
Scheurer
Christian
C
Wittlin
Sergio
S
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use; D053626:Atovaquone / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D021261:Parasitic Sensitivity Tests; D010545:Peroxides / Q000494:pharmacology* / Q000627:therapeutic use; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D013141:Spiro Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines
D000962:Antimalarials; D000077549:Artemether; D037621:Artemisinins; D053626:Atovaquone; D006573:Heterocyclic Compounds, 1-Ring; D010545:Peroxides; D011739:Pyrimethamine; D011804:Quinolines; D013141:Spiro Compounds; C489136:arterolane; C034759:piperaquine; D010879:Piperazines