Specific pharmacokinetic interaction between lumefantrine and monodesbutyl-benflumetol in Plasmodium falciparum.
The blood schizontocidal activity of lumefantrine, monodesbutyl-benflumetol (DBB) and a 999:1 combination of both compounds has been investigated in 26 fresh isolates of Plasmodium falciparum from northwestern Thailand, using the WHO standard protocol Mark II for determining the inhibition of schizont maturation. The geometric mean cut-off concentrations of schizont maturation (GMCOC) were 943.2 nM for lumefantrine, 146.3 nM for DBB and 182.2 nM for the 999:1 combination of lumefantrine and DBB. The EC(50) values were 27.3 nM for lumefantrine, 5.7 nM for DBB, and 16.5 nM for the combination, and the EC(90) values 163.1 nM for lumefantrine, 44.1 nM for DBB, and 78.3 nM for the combination. Despite the very low concentration in the combination, DBB exerted significant synergistic activity with lumefantrine that was strongest at the EC(90) and EC(99) levels. Correlation analysis indicates that DBB is the leading determinant for the activity of the combination.
Starzengruber
Peter
P
Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
Wernsdorfer
Gunther
G
Parizek
Maria
M
Rojanawatsirivet
Chaiporn
C
Kollaritsch
Herwig
H
Wernsdorfer
Walther H
WH
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage* / Q000097:blood*; D005449:Fluorenes / Q000008:administration & dosage* / Q000097:blood*; D006801:Humans; D007928:Lethal Dose 50; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology; D015996:Survival Rate; D016896:Treatment Outcome
D000962:Antimalarials; D004983:Ethanolamines; D005449:Fluorenes; D000078102:Lumefantrine