In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents

Abstract

The in-vitro activities of pyronaridine, amodiaquine, chloroquine and quinine were evaluated against 161 isolates of Plasmodium falciparum from Senegal (Dielmo, Ndiop and Pikine), using an isotopic, micro, drug susceptibility test. The mean IC50 values (50% inhibitory concentration) for pyronaridine and amodiaquine were 3.8 nM (95% confidence interval (95% CI), 3.1-4.4) and 12.0 nM (95% CI, 10.0-14.0 nM), respectively. Pyronaridine and amodiaquine were more active than chloroquine against susceptible parasites. However, both drugs were significantly less active (P < 0.002 and P < 0.025) against chloroquine-resistant isolates than against chloroquine-susceptible isolates. Based on statistical calculation using the present data (mean IC50 + 2 S.D.), the cut-off value for in-vitro susceptibility to pyronaridine is IC50 < 15 nM; for eight isolates (5%) the IC50 was > 15 nM. No isolates tested showed resistance to amodiaquine (IC50 > 80 nM). Significant positive correlations, suggesting cross-resistance among these drugs in vitro, were found between pyronaridine and chloroquine (r2 = 0.19, P < 0.001), pyronaridine and quinine (r2 = 0.44, P < 0.001), pyronaridine and amodiaquine (r2 = 0.34, P < 0.001), amodiaquine and chloroquine (r2 = 0.14, P < 0.001), and amodiaquine and quinine (r2 = 0.21, P < 0.001). The present in-vitro findings require comparison with clinical studies.