Synergism of benflumetol and artemether in Plasmodium falciparum

Using a continuous in vitro culture system, the sensitivity of Plasmodium f alciparum to artemether and a new antimalarial drug, benflumetol (lumefantr ine), alone and in combination, was investigated with a multiresistant stra in (T-996) from Thailand and a chloroquine-resistant strain (LS-21) from In dia. Both strains showed similar 50% inhibitory concentration (IC50) levels with artemether alone or benflumetol alone, but the IC90 was higher in str ain T-996 compared with strain LS-21: for artemether, 34.45 and 7.11 nmol/L (10.28 and 2.12 ng/ml of erythrocyte-medium mixture [EMM]), and for benflu metol, 293.03 and 95.61 nmol/L (154.69 and 50.47 ng/ml of EMM). When tested in association artemether:benflumetol (mol:mol) ratios between 100:1 and 1 :100, substantial synergism was seen in both strains, especially at the IC9 0 and IC99 levels. This phenomenon resembles the synergistic interaction of artemisinin derivatives and mefloquine, first observed in laboratory model s and later confirmed in clinical experience.