Comparison of beta-artemether and beta-arteether against malaria parasites in vitro and in vivo.
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.
Shmuklarsky
M J
MJ
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC.
Klayman
D L
DL
Milhous
W K
WK
Kyle
D E
DE
Rossan
R N
RN
Ager
A L
AL
Tang
D B
DB
Heiffer
M H
MH
Canfield
C J
CJ
Schuster
B G
BG
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
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D002738:Chloroquine; D000077549:Artemether; D015767:Mefloquine; C055141:artemotil