ABSTRACT
Blood schizontocidal effect of antimalarials were compared by 4-day suppressive test with an extended observation period of 31 days. On a drug-sensitive Plasmodium berghei ANKA strain, pyronaridine (PND) exhibited the best effect, followed by amodiaquine (ADQ), mefloquine (MFQ), and qinghaosu (QHS). On a moderately chloroquine-resistant P. berghei NS line, the order of effects was the same, PND greater than ADQ greater than MFQ greater than QHS. On a highly pyronaridine-resistant P. berghei RP line, ADQ, MFQ and QHS showed cross resistance with PND.
Subject(s)
Amodiaquine/administration & dosage , Animals , Antimalarials/administration & dosage , Artemisinins , Drug Administration Schedule , Drug Evaluation, Preclinical , Drug Resistance , Female , Malaria/drug therapy , Male , Mefloquine/administration & dosage , Mice , Naphthyridines/administration & dosage , Plasmodium berghei , Sesquiterpenes/administration & dosageABSTRACT
The triple combination of pyronaridine, sulfadoxine and pyrimethamine which has been proven to be efficient in delaying emergence of drug resistance of rodent malarial parasites was further studied for potential application to malaria control. The antimalarial effect of the triple combination on Plasmodium berghei ANKA-infected mice and the toxic effects in mice and rats were additive. A single dose of pyronaridine 500 mg in combination with sulfadoxine, 1000 or 1500 mg, and pyrimethamine, 50 or 75 mg, given to 72 acute falciparum malaria patients resulted in a 100% cure rate with nil or mild side effects, and no recrudescence of asexual parasite over 4-week follow-up. Preliminary experiments on the drug effect on sporogony showed that the drug combination at the dose used could not completely interrupt the sporozoite formation although many retarded oocysts were found.