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Am. J. Trop. Med. Hyg., 40(1), 1989, pp. 7-11
Copyright © 1989 by The American Society of Tropical Medicine and Hygiene

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A Comparison of the in Vitro Activities of Amodiaquine and Desethylamodiaquine against Isolates of Plasmodium falciparum

G. E. Childs, E. F. Boudreau, W. K. Milhous*, T. Wimonwattratee, N. Pooyindee, L. Pang AND D. E. Davidson, Jr.*
U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
* Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307

The antimalarial activities of amodiaquine, the desethyl metabolite of amodiaquine, chloroquine, and mefloquine were evaluated against 35 field isolates of Plasmodium falciparum collected from eastern Thailand, October–December 1985, to define patterns of cross-resistance among these compounds. The assay system was based on the in vitro inhibition of schizont maturation. The parasites were generally sensitive to mefloquine (mean 50%-inhibitory concentrations = 9.98 nM) and highly resistant to chloroquine (IC50 = 313 nM). The mean in vitro activity of desethylamodiaquine (67.5 nM) was approximately 3.5 times lower than that of amodiaquine (18.2 nM). There was a significant rank-order correlation between the IC50s of desethylamodiaquine and chloroquine, but not between amodiaquine and chloroquine, which suggests that the apparent cross-resistance between chloroquine and amodiaquine observed in clinical studies may be more closely related to the cross-resistance between chloroquine and the metabolite rather than between chloroquine and the parent compound. Isolates with IC50 values of amodiaquine >20 nM demonstrated a high degree of correlation with values of desethylamodiaquine; however, it was not possible to accurately predict the sensitivity to desethylamodiaquine of isolates which had IC50 values of amodiaquine of <20 nM.

Accepted for publication July 22, 1988.




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Copyright © 1989 by the American Society of Tropical Medicine and Hygiene.