title: Comparison of beta-artemether and beta-arteether against malaria parasites in vitro and in vivo.
abstract: The antimalarial activity of beta-artemether and beta-arteether was compared in three test systems: in vitro against chloroquine-resistant and chloroquine-sensitive Plasmodium falciparum parasites, in mice infected with P. berghei, and in Aotus monkeys infected with chloroquine-resistant P. falciparum. In vitro, the mean 50% inhibitory concentration (IC50) for beta-artemether was 1.74 nM (range 1.34-1.81 nM), and this value for beta-arteether was 1.61 nM (range 1.57-1.92 nM). They were approximately 2.5-fold more potent than artemisinin, which had a mean IC50 of 4.11 nM (range 3.36-4.60 nM). In the mouse model, the 50% curative doses (CD50) of beta-artemether and beta-arteether had a mean value of 55 mg/kg (32-78 mg/kg). The 50% effective curative doses (ED50) in the Aotus monkey were 7.1 mg/kg (95% confidence interval [CI] = 3.7-13.5) for beta-artemether and 11.8 mg/kg (95% CI = 6.5-21.3) for beta-arteether. Overall, the activities of the two drugs were comparable.
authors: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC.
authors: M J
authors: MJ
authors: Shmuklarsky
authors: D L
authors: DL
authors: Klayman
authors: W K
authors: WK
authors: Milhous
authors: D E
authors: DE
authors: Kyle
authors: R N
authors: RN
authors: Rossan
authors: A L
authors: AL
authors: Ager
authors: D B
authors: DB
authors: Tang
authors: M H
authors: MH
authors: Heiffer
authors: C J
authors: CJ
authors: Canfield
authors: B G
authors: BG
authors: Schuster
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D001029:Aotus trivirgatus; D000077549:Artemether; D037621:Artemisinins; D002738:Chloroquine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008288:Malaria / Q000188:drug therapy; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000494:pharmacology; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D002738:Chloroquine; D000077549:Artemether; D015767:Mefloquine; C055141:artemotil