In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine

The in vitro activity of pyronaridine was evaluated against 62 isolates of Plasmodium falciparum from Libreville, Gabon using an isotopic, drug suscep tibility microtest and was compared with amodiaquine, chloroquine, quinine, and halofantrine activities. The mean 50% inhibitory concentration (IC50) values of the 62 isolates from Gabon to pyronaridine was 3.0 nM (95% confid ence interval [CI] = 2.1-3.9). Pyronaridine was less potent against chloroq uine-resistant isolates than chloroquine-susceptible isolates but more pote nt than chloroquine against chloroquine-resistant parasites. The cut-off va lue for in vitro reduced susceptibility to pyronaridine was an IC50 > 15 nM . Two isolates (3%) showed an IC50 > 15 nM. A significant positive correlat ion was found between the activities of pyronaridine and chloroquine (r(2) = 0.26, P < 0.001), pyronaridine and quinine (r(2) = 0.36, P < 0.001), pyro naridine and amodiaquine (r(2) = 0.55, P < 0.001), and pyronaridine and hal ofantrine (r(2) = 0.50, P < 0.001). This correlation suggests in vitro cros s-resistance or at least in vitro cross-susceptibility, which is not necess arily predictive of cross-resistance in vivo. The present in vitro findings require comparison with those of clinical studies.