In vitro activity of lumefantrine (benflumetol) against clinical isolates of Plasmodium falciparum in Yaoundé, Cameroon

Abstract

The in vitro antimalarial activity of the new Chinese synthetic drug, lumefantrine, also known as benflumetol (a fluorene derivative belonging to the aminoalcohol class), was determined by an isotopic microtest against 61 fresh clinical isolates of Plasmodium falciparum and compared with that of other established antimalarial agents. The geometric mean 50% inhibitory concentration of lumefantrine was 11.9 nmol/liter (95% confidence intervals, 10.4 to 13.6 nmol/liter; range, 3.3 to 25.6 nmol/liter). The in vitro activities of lumefantrine against the chloroquine-sensitive and the chloroquine-resistant isolates did not differ (P > 0.05). There was a significant positive correlation of responses between lumefantrine and two other aminoalcohols studied, mefloquine (r = 0.688) and halofantrine (r = 0.677), and between lumefantrine and artesunate (r = 0.420), suggesting a potential for in vitro cross-resistance. Our data suggest high in vitro activity of lumefantrine, comparable to that of mefloquine, and are in agreement with the promising results of preliminary clinical trials.

FIG. 1

Chemical structures of chloroquine, mefloquine, and lumefantrine.

FIG. 2

Distribution of IC₅₀ of chloroquine (CQ), monodesethylamodiaquine (mAQ), quinine (QU), mefloquine (MQ), halofantrine (HF), artesunate (AR), pyrimethamine (PY), and lumefantrine (LF) against Cameroonian P. falciparum isolates.

FIG. 3

Correlation of in vitro responses, expressed as logarithmic IC₅₀, to lumefantrine and mefloquine (black circles; coefficient of correlation [r] = 0.688; n = 44), lumefantrine and halofantrine (open circles; r = 0.677; n = 61), and lumefantrine and artesunate (black squares; r = 0.420; n = 61).