title: Comparative study on the in vitro activity of lumefantrine and desbutyl-benflumetol in fresh isolates of Plasmodium vivax from Thailand.
abstract: The occurrence of chloroquine resistance in Plasmodium vivax underlines the need for monitoring the drug response of this important malaria parasite and for the evaluation of alternative therapeutic agents. In-vitro methods facilitate these tasks. This investigation employed a recently developed in-vitro micro-technique and validated it for lumefantrine and desbutyl-benflumetol, a compound that was initially considered a metabolite of lumefantrine. The studies were conducted in 2001 at Mae Sot, a town situated in northwestern Thailand near the border to Myanmar. Parallel in-vitro tests with lumefantrine and desbutyl-benflumetol were carried out with 53 fresh isolates of P. vivax. For both compounds, the parasite showed a homogenous, log-normal inhibition pattern with nearly parallel log-probit regressions. The geometric mean drug concentrations effecting complete growth inhibition were 2361 nM for lumefantrine and 187 nM for desbutyl-benflumetol. With p=3.264 x 10(-18) the difference was highly significant. The EC50 and EC90 values for lumefantrine, 17.6 nM and 448.5 nM, respectively, were much higher as compared to those determined for desbutyl-benflumetol, with 1.5 nM and 39.7 nM. This difference expressed itself in a highly significant Power Ratio (PR) of 11.0. The activity of desbutyl-benflumetol in P. vivax exceeds that of lumefantrine by one order of magnitude, suggesting a high, hitherto unexploited therapeutic potential of desbutyl-benflumetol.
authors.affiliation: Division of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria.
authors.forename: Daniela K
authors.initials: DK
authors.lastname: Pirker-Krassnig
authors.forename: Gunther
authors.initials: G
authors.lastname: Wernsdorfer
authors.forename: Jeeraphat
authors.initials: J
authors.lastname: Sirichaisinthop
authors.forename: Chaiporn
authors.initials: C
authors.lastname: Rojanawatsirivet
authors.forename: Herwig
authors.initials: H
authors.lastname: Kollaritsch
authors.forename: Walther H
authors.initials: WH
authors.lastname: Wernsdorfer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D016009:Chi-Square Distribution; D002648:Child; D016001:Confidence Intervals; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000078102:Lumefantrine; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D013785:Thailand
chemical_list: D000962:Antimalarials; D004983:Ethanolamines; D005449:Fluorenes; C435716:desbutylbenflumetol; D000078102:Lumefantrine