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|Title:||Comparative study on the in vitro activity of lumefantrine and desbutyl-benflumetol in fresh isolates of Plasmodium vivax from Thailand|
|Authors:||Daniela K. Pirker-Krassnig|
Walther H. Wernsdorfer
Medizinische Universitat Wien
Thailand Ministry of Public Health
Institute for Specific Prophylaxis and Tropical Medicine
|Citation:||Wiener Klinische Wochenschrift, Supplement. Vol.116, No.4 SUPPL. (2004), 47-52|
|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 × 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.|
|Appears in Collections:||Scopus 2001-2005|
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