IN-VITRO ACTIVITY OF PYRONARIDINE AND AMODIAQUINE AGAINST AFRICAN ISOLATES (SENEGAL) OF PLASMODIUM-FALCIPARUM IN COMPARISON WITH STANDARD ANTIMALARIAL AGENTS

The in-vitro activities of pyronaridine, amodiaquine, chloroquine and quinine were evaluated against 161 isolates of Plasmodium falciparum f rom Senegal (Dielmo, Ndiop and Pikine), using an isotopic, micro, drug susceptibility test. The mean IC50 values (50% inhibitory concentrati on) for pyronaridine and amodiaquine were 3.8 nM (95% confidence inter val (95% CI), 3.1-4.4) and 12.0 nM (95% CI, 10.0-14.0 nM), respectivel y. Pyronaridine and amodiaquine were more active than chloroquine agai nst susceptible parasites. However, both drugs were significantly less active (P < 0.002 and P < 0.025) against chloroquine-resistant isolat es 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 re sistance to amodiaquine (IC50 > 80 nM). Significant positive correlati ons, suggesting cross-resistance among these drugs in vitro, were foun d between pyronaridine and chloroquine (r(2) = 0.19, P < 0.001), pyron aridine and quinine (r(2) = 0.44, P < 0.001), pyronaridine and amodiaq uine (P = 0.34, P < 0.001), amodiaquine and chloroquine (r(2) = 0.14, P < 0.001), and amodiaquine and quinine (r(2) = 0.21, P < 0.001). The present in-vitro findings require comparison with clinical studies.