title: A comparison of the in vitro activities of amodiaquine and desethylamodiaquine against isolates of Plasmodium falciparum.
abstract: 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 greater than 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 less than 20 nM.
authors.affiliation: U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
authors.forename: G E
authors.initials: GE
authors.lastname: Childs
authors.forename: E F
authors.initials: EF
authors.lastname: Boudreau
authors.forename: W K
authors.initials: WK
authors.lastname: Milhous
authors.forename: T
authors.initials: T
authors.lastname: Wimonwattratee
authors.forename: N
authors.initials: N
authors.lastname: Pooyindee
authors.forename: L
authors.initials: L
authors.lastname: Pang
authors.forename: D E
authors.initials: DE
authors.lastname: Davidson
mesh_terms: D000655:Amodiaquine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D015767:Mefloquine; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology; D013785:Thailand
chemical_list: D000962:Antimalarials; D011804:Quinolines; D000655:Amodiaquine; C047386:desethylamodiaquine; D002738:Chloroquine; D015767:Mefloquine