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Pharmacodynamic interaction between monodesbutyl-benflumetol and artemisinin as well as proguanil in Plasmodium falciparum in vitro
Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Austria.
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Bureau of Vector Borne Diseases, Ministry of Public Health, Nonthaburi, Thailand.
Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Austria.
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2008 (English)In: Wiener Klinische Wochenschrift, ISSN 0043-5325, E-ISSN 1613-7671, Vol. 120, no 4, 90-94 p.Article in journal (Refereed) Published
Abstract [en]

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. © 2008 Springer-Verlag.

Abstract [de]

Die Sensibilität von Plasmodium falciparum gegenüber Artemisinin, Monodebutyl-Benflumetol und einer 1:3 Kombination beider Stoffe wurde bei 51 frischen Parasitenisolaten untersucht. Obwohl der Vergleich zwischen den Werten für volle Hemmung durch Artemisinin allein (63,33 nM), DBB allein (50,15 nM) und die Kombination (23,92 nM) klar synergistisches Verhalten zwischen Artemisinin und DBB anzeigte, war dies weniger ersichtlich beim Vergleich der Log-Probit Regressionen. Ferner stiegen die geometrischen Mittelwerte der Summe der fraktionellen Hemmkonzentrationen (SFIC) mit Zunahme der effektiven Hemmkonzentrationen (EC). Die Interaktion zwischen DBB und Proguanil wurde mittels einer 3:1 m/m Kombination beider Stoffe an 24 frischen Isolaten von P. falciparum untersucht. Proguanil allein hatte schwache blutschizontozide Wirkung. Die Log-Probit Regressionen zeigten für die Kombination höhere Aktivität im Vergleich zu DBB allein. Die SFIC Werte waren im Bereich von mäßigem Synergismus. Durch den Zusatz von Proguanil konnte die Wirksamkeit von DBB nahezu verdoppelt werden. Dies könnte bei möglicher künftiger therapeutischer oder prophylaktischer Anwendung von DBB vorteilhaft sein.

Place, publisher, year, edition, pages
Springer, 2008. Vol. 120, no 4, 90-94 p.
Keyword [en]
Artemisinin, Monodesbutyl-benflumetol, Plasmodium falciparum, Proguanil, Synergism
National Category
Biomedical Laboratory Science/Technology
URN: urn:nbn:se:liu:diva-50120DOI: 10.1007/s00508-008-1038-xPubMedID: 19066781ScopusID: 2-s2.0-57849146651OAI: diva2:271016
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2015-11-19Bibliographically approved

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Raffelsberger, Jens
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