Journal of Antimicrobial Chemotherapy, Vol 42, 333-339, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
B Pradines, A Tall, D Parzy, A Spiegel, T Fusai, R Hienne, JF Trape and JC Doury
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.
ORIGINAL ARTICLES
In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents
Unite de Parasitologie, Institut de Medecine Tropicale du Service de Sante des Armees, Le Pharo, Marseille, France.
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