title: Pharmacodynamic interaction between monodesbutyl-benflumetol and artemisinin as well as proguanil in Plasmodium falciparum in vitro.
abstract: The sensitivity of Plasmodium falciparum against artemisinin, monodebutyl-benflumetol (DBB) and a 1:3 m/m combination of both compounds was assessed in 51 fresh parasite isolates. Although a comparison between fully inhibitory concentrations (GMCOC) of artemisinin alone (63.33 nM), DBB alone (50.15 nM) and the combination (23.92 nM) indicated significant synergism between artemisinin and DBB, this was less evident when comparing the log-probit regressions. Moreover, the geometric mean values of the fractional inhibitory concentrations (SFIC) showed a rising tendency with increasing EC level. In a study comprising 24 fresh isolates of P. falciparum, the interaction between DBB and proguanil was explored with a 3:1 m/m combination of both compounds. Proguanil alone showed weak blood schizontocidal activity. The log-probit regressions indicated higher activity of the combination as compared to DBB alone. The SFIC values indicated moderate synergism between DBB and proguanil that could be an advantage in an eventual therapeutic and prophylactic use of DBB.
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Austria. jens.raffelsberger@lio.se
authors.forename: Jens
authors.initials: J
authors.lastname: Raffelsberger
authors.forename: Gunther
authors.initials: G
authors.lastname: Wernsdorfer
authors.forename: Jeeraphat
authors.initials: J
authors.lastname: Sirichaisinthop
authors.forename: Herwig
authors.initials: H
authors.lastname: Kollaritsch
authors.forename: Kanungnit
authors.initials: K
authors.lastname: Congpuong
authors.forename: Walther H
authors.initials: WH
authors.lastname: Wernsdorfer
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D005449:Fluorenes / Q000494:pharmacology*; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D002727:Proguanil / Q000494:pharmacology*; D013785:Thailand; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; C435716:desbutylbenflumetol; C031327:artemisinin; D002727:Proguanil