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Pharmacodynamic interaction between mefloquine and retinol in Plasmodium falciparum in vitro

Pharmakodynamische Interaktion zwischen Mefloquin und Retinol bei Plasmodium falciparum in vitro

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Zusammenfassung

Mefloquin, ein 4-Chinolinmethanol, wurde in Thailand zur Behandlung der Malaria Tropica eingeführt nachdem Plasmodium falciparum fast universelle Resistenz gegen die 4-Aminochinoline und Folsäurehemmer entwickelt hatte. Obwohl auch Resistenz gegen Mefloquin zu einem Problem wurde, war Artemisinin-basierende Kombinationstherapie (ACT) mittels Mefloquine und Artesunat bis vor kurzem ausreichend wirksam. Da die Wirkung von Chinin, einem anderen 4-Chinolinmethanol, durch Retinol erheblich verstärkt wird, war eine Erweiterung der Untersuchungen auf Mefloquin naheliegend. Die Interaktion zwischen Mefloquin und Retinol, letzteres bei Konzentrationen entsprechend der 50., 65. und 80. Perzentile der physiologischen Serumkonzentrationen bei gesunden Erwachsenen, wurde bei 37 frischen Isolaten von P. falciparum untersucht. Die mittleren IC50, IC90 und IC99 Werte für Mefloquin lagen bei 1,76, 9,81 und 39,78 μM, jene für Mefloquin + Retinol "niedrig" bei 0,33, 1,37 und 4,33 μM, jene für Mefloquin + Retinol "mittel" bei 0,29, 1,15 und 3,48 μM, und jene für Mefloquin + Retinol "hoch" bei 0,20, 0,85 und 2,70 μM. Evidenz für beträchtlichen Synergismus zwischen Mefloquin und Retinol bei P. falciparum war hoch signifikant.

Summary

Mefloquine, a 4-quinolinemethanol derivative, was introduced in Thailand after Plasmodium falciparum had acquired almost universal resistance to the 4-aminoquinolines and antifols. However, also resistance to mefloquine has become an increasing problem, but artemisinin-based combination therapy (ACT) with mefloquine and artesunate remained until recently sufficiently effective. Since synergistic interaction between quinine, another 4-quinolinemethanol, with retinol was observed earlier, the investigations were expanded to mefloquine. The interaction between mefloquine and retinol at concentrations equal to the 50th, 65th and 80th percentile of the physiological retinol levels in healthy adults was determined in 37 fresh isolates of P. falciparum. The mean IC50, IC90 and IC99 values for mefloquine were 1.76, 9.81 and 39.78 μM, those for mefloquine + retinol "low" 0.33, 1.37 and 4.33 μM, those for mefloquine + retinol "medium" 0.29, 1.15 and 3.48 μM, and those for mefloquine + retinol "high" 0.20, 0.85 and 2.70 μM. Evidence for strong synergism between mefloquine and retinol in P. falciparum was highly significant.

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Authors and Affiliations

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

    Maria Gruber, Ursula Wiedermann & Walther H. Wernsdorfer

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

    Gunther Wernsdorfer

  3. Bureau of Vector-borne Disease Control, Ministry of Public Health of Thailand, Nonthaburi, Thailand

    Wichai Satimai & Kanungnit Congpuong

Authors
  1. Maria Gruber
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  2. Gunther Wernsdorfer
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  3. Wichai Satimai
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  4. Ursula Wiedermann
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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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Gruber, M., Wernsdorfer, G., Satimai, W. et al. Pharmacodynamic interaction between mefloquine and retinol in Plasmodium falciparum in vitro. Wien Klin Wochenschr 121 (Suppl 3), 27–31 (2009). https://doi.org/10.1007/s00508-009-1231-6

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  • DOI: https://doi.org/10.1007/s00508-009-1231-6

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