Plasmodium yoelii nigeriensis (MDR)-efficacy of oral pyronaridine against multidrug-resistant malaria in Swiss mice.
A multidrug-resistant strain of Plasmodium yoelii nigeriensis (MDR) showing a wide spectrum of resistance to chloroquine, amodiaquine, mepacrine, mefloquine, halofantrine, quinine, and quinidine was used in this study for in vivo evaluation of the blood schizontocidal activity of pyronaridine, a topoisomerase II inhibitor, in Swiss mice. The parasite produces 100% lethal infection in mice. The drug was administered orally once a day from day 0 onward. The initial studies showed that low doses of pyronaridine (0.625 to 5.0 mg base/kg x9 days) did not completely control blood-induced P. yoelii nigeriensis infection. Finally a series of doses of pyronaridine ranging from 1.25 to 30.0 mg/kg administered orally for 7 consecutive days were evaluated and in spite of high level of resistance to standard antimalarials, the parasite P. yoelii nigeriensis has shown complete susceptibility to pyronaridine (15 mg/kg dose x7 days). The present paper also compares the merits of a single MDR strain vs a battery of different resistant lines for quick antimalarials screening.
Tripathi
R
R
Division of Microbiology, Central Drug Research Institute, Lucknow, 226001, India.
Umesh
A
A
Mishra
M
M
Puri
S K
SK
Dutta
G P
GP
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D009287:Naphthyridines / Q000494:pharmacology* / Q000627:therapeutic use; D010967:Plasmodium yoelii / Q000187:drug effects*; D059005:Topoisomerase II Inhibitors
D000962:Antimalarials; D009287:Naphthyridines; D059005:Topoisomerase II Inhibitors; C027871:pyronaridine