title: In vitro activity of monodesethylamodiaquine and amopyroquine against African isolates and clones of Plasmodium falciparum.
abstract: The in vitro activity of monodesethylamodiaquine and amopyroquine was evaluated against chloroquine-susceptible and chloroquine-resistant African clones of Plasmodium falciparum. The chloroquine-resistant clone (50% inhibitory concentration [IC50] = 1,630 nM) was 26 and 3.7 times less susceptible to monodesethylamodiaquine and amopyroquine, respectively, than the chloroquine-susceptible clone (IC50 = 36.5 nM). Cross-resistance patterns of chloroquine, monodesethylamodiaquine, and amopyroquine were determined against 62 African isolates of P. falciparum obtained from imported cases of malaria in France, using an isotopic semimicro drug susceptibility test. Chloroquine-resistant isolates (n = 38) were significantly less susceptible to both monodesethylamodiaquine (IC50 = 74.8 nM) and amopyroquine (IC50 = 18.9 nM), as compared with the 24 chloroquine-susceptible isolates (IC50 = 28.2 nM and 16.1 nM, respectively). A significant positive correlation was found between chloroquine and monodesethylamodiaquine (r = 0.903) and between chloroquine and amopyroquine (r = 0.371), indicating in vitro cross-resistance among these drugs. These in vitro results suggest that the clinical response to amodiaquine and amopyroquine needs to be closely monitored in Africa.
authors.affiliation: Centre National de Reference pour la Chimiosensibilite du Paludisme, Hopital Bichat-Claude Bernard, Paris, France.
authors.forename: L K
authors.initials: LK
authors.lastname: Basco
authors.forename: J
authors.initials: J
authors.lastname: Le Bras
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology*; D000655:Amodiaquine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects*; D012044:Regression Analysis
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D000655:Amodiaquine; C047386:desethylamodiaquine; D002738:Chloroquine; C009846:amopyroquine