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Synergism between monodesbutyl-benflumetol and artemisinin in Plasmodium falciparum in vitro

Synergismus zwischen Monodesbutyl-Benflumetol und Artemisinin bei Plasmodium falciparum in vitro

Wiener klinische Wochenschrift volume 120, pages 80–84 (2008)Cite this article

Zusammenfassung

In 34 frischen Isolaten von Plasmodium falciparum wurde die Sensibilität gegenüber Artemisinin, Monodesbutyl-Benflumetol (DBB) und einer 1:1 m/m Kombination beider Stoffe ermittelt. Auf molarer Basis war die Kombination am wirksamsten, vor DBB und Artemisinin. Die geometrischen Mittelwerte für volle Hemmung lagen bei 49,25 nM für die Kombination, 279,12 nM für DBB und 494,05 nM für Artemisinin. Der Unterschied der Wirksamkeit der Kombination gegenüber Artemisinin allein und DBB allein war hoch signifikant. Die Interaktionsanalyse ergab mäßigen Synergismus bei der EC50 und hochgradigen Synergismus bei EC90 und EC99. Bei den einzelnen Isolaten zeigten Höhe der EC und Grad des Synergismus signifikante umgekehrte Korrelation. Der Synergismus ist daher bei Isolaten mit reduzierter Empfindlichkeit gegenüber Artemisinin und DBB am stärksten ausgeprägt.

Summary

The sensitivity to artemisinin, monodesbutyl-benflumetol (DBB) and a 1:1 m/m combination of the two compounds was successfully investigated on 34 fresh isolates of Plasmodium falciparum. On a molar basis the combination was most active, followed by DBB and artemisinin. The geometric mean concentrations effecting full inhibition (GMCOC) were 49.25 nM for the combination, 279.12 nM for DBB, and 494.05 for artemisinin. The difference between the efficacy of the combination and that of its components was highly significant. Interaction between artemisinin and DBB showed moderate synergism at the EC50 and strong synergism at EC90 and EC99. The individual parasite isolates showed a significant inverse correlation between the ECs and the degree of synergism. Positive specific pharmacodynamic interaction was therefore most marked in isolates with reduced sensitivity against artemisinin and DBB.

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Affiliations

  1. Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Austria

    Gernot Müller, Peter Starzengruber & Walther H. Wernsdorfer

  2. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

    Gunther Wernsdorfer & Walther H. Wernsdorfer

  3. Bureau of Vector Borne Diseases, Ministry of Public Health, Nonthaburi, Thailand

    Jeeraphat Sirichaisinthop & Kanungnit Congpuong

Authors
  1. Gernot Müller
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  2. Gunther Wernsdorfer
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  3. Jeeraphat Sirichaisinthop
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  4. Peter Starzengruber
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  5. Kanungnit Congpuong
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  6. Walther H. Wernsdorfer
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Correspondence to Walther H. Wernsdorfer.

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Müller, G., Wernsdorfer, G., Sirichaisinthop, J. et al. Synergism between monodesbutyl-benflumetol and artemisinin in Plasmodium falciparum in vitro. Wien Klin Wochenschr 120, 80–84 (2008). https://doi.org/10.1007/s00508-008-1034-1

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  • DOI: https://doi.org/10.1007/s00508-008-1034-1

Keywords

  • Plasmodium falciparum
  • Desbutyl-benflumetol
  • Artemisinin
  • Synergism