Synergism of benflumetol and artemether in Plasmodium falciparum.

M Hassan Alin Department of Pharmacy, Biomedical Centre, Uppsala University, Sweden.

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A Björkman Department of Pharmacy, Biomedical Centre, Uppsala University, Sweden.

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W H Wernsdorfer Department of Pharmacy, Biomedical Centre, Uppsala University, Sweden.

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DOI:
https://doi.org/10.4269/ajtmh.1999.61.439
Volume/Issue:
Volume 61: Issue 3
Page(s):
439–445
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Using a continuous in vitro culture system, the sensitivity of Plasmodium falciparum to artemether and a new antimalarial drug, benflumetol (lumefantrine), alone and in combination, was investigated with a multiresistant strain (T-996) from Thailand and a chloroquine-resistant strain (LS-21) from India. Both strains showed similar 50% inhibitory concentration (IC50) levels with artemether alone or benflumetol alone, but the IC90 was higher in strain 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 benflumetol, 293.03 and 95.61 nmol/L (154.69 and 50.47 ng/ml of EMM). When tested in association at artemether:benflumetol (mol: mol) ratios between 100:1 and 1:100, substantial synergism was seen in both strains, especially at the IC90 and IC99 levels. This phenomenon resembles the synergistic interaction of artemisinin derivatives and mefloquine, first observed in laboratory models and later confirmed in clinical experience.

Author Notes

Published Online:
Sep 1999
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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