Zusammenfassung
Die vorliegende Studie wurde im Nordwesten Thailands in einem von Multiresistenz betroffenen Gebiet durchgeführt. Sie hatte das Ziel, die blutschizontozide Wirkung von Atovaquon (ATO), Retinol (RET) and deren Kombination (ATO-RET) bei Retinolanteilen entsprechend der 50., 65. und 80. Perzentile der physiologischen Serum-Retinolspiegel zu prüfen. Die in vitro Tests wurden gemäß WHO Standardprotokoll Mark II zur Messung der Hemmung der Schizontenreifung bei Plasmodium falciparum durchgeführt. Ergebnisse für alle 5 parallele Testreihen liegen für 26 frische Isolate vor. Die EC50 Werte für Atovaquon, Retinol und für Atovaquon in ATO-RET "low", "medium" und "high" lagen bei 3,1 nM, 561,8 nM, 0,9 nM, 0,7 nM und 0,5 nM, jene der EC90 bei 33,7 nM, 9338,6 nM, 25,3 nM, 8,9 nM und 5,4nM. Die geometrischen Mittelkonzentrationen für volle Hemmung der Schizontenreifung für Atovaquon allein und für Atovaquon in den ATO-RET Kombinationen "low", "medium" und "high" waren 282,5 nM, 79,0 nM. 38,7 nM und 23,7 nM. Diese Ergebnisse und jene der Berenbaum Analyse der fraktionellen Hemmkonzentrationen weisen auf eine erhebliche synergistische pharmakodynamische Interaktion zwischen Atovaquon und Retinol hin. Dies legt nahe, dass die spezifische Wirkung von Atovaquon durch eine Anhebung der Retinolspiegel im physiologischen Bereich verstärkt werden könnte.
Summary
The study has been conducted with the objective of assessing the blood schizontocidal activities of atovaquone (ATO), retinol (RET) and combinations of both (ATO-RET) at set retinol concentrations corresponding to the 50th, 65th and 80th percentile of the physiological serum retinol levels. The in vitro tests followed the WHO standard protocol Mark II for measuring the inhibition of schizont maturation in Plasmodium falciparum. Valid results for all 5 test lines were obtained with 26 fresh parasite isolates from northwestern Thailand, an area affected by multidrug-resistance. The EC50 values for atovaquone, retinol and for ATO in ATO-RET low, medium and high were 3.1 nM, 561.8nM, 0.85 nM, 0.73 nM and 0.45 nM, respectively, the EC90 values 33.7 nM, 9338.6 nM, 25.31 nM, 8.89 nM, and 5.42 nM. The geometric mean cut-off concentrations of schizont maturation of atovaquone alone and for atovaquone in ATO-RET low, medium and high were 282.5nM, 79.0 nM, 38.7 nM and 23.7 nM, respectively. These results and those of the Berenbaum analysis based on the fractional inhibitory concentrations indicate synergistic pharmacodynamic interaction between atovaquone and retinol, a phenomenon suggesting that the antimalarial activity of atovaquone could be enhanced by supplementation with retinol.
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Exner, B., Wernsdorfer, G., Sirichaisinthop, J. et al. Synergistic interaction between atovaquone and retinol in Plasmodium falciparum in vitro . Wien Klin Wochenschr 119 (Suppl 3), 45–52 (2007). https://doi.org/10.1007/s00508-007-0868-2
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DOI: https://doi.org/10.1007/s00508-007-0868-2