Oxygen Enhances the Antimalarial Activity of the Imidazoles

Michael A. Pfaller, Donald J. Krogstad · American Journal of Tropical Medicine and Hygiene · 1983

We have previously reported the antimalarial activity of imidazoles and amphotericin B against chloroquine-resistant Plasmodium falciparum. We now report the enhancement of imidazole activity in an atmosphere with 17-18% oxygen (the candle jar) vs. 3% or 0.3% oxygen. Based on both morphologic and radiometric testing, smaller amounts of the imidazoles were required to inhibit parasite growth by 50% in the candle jar vs. 3% or 0.3% oxygen. The use of older (more oxidant-sensitive) red cells also enhanced the antimalarial activity of ketoconazole. Neither increased concentrations of oxygen nor the use of older red cells affected the activity of amphotericin B. These results suggest that the imidazoles may exert their antimalarial effect by increasing the oxidant stress on the red cell-parasite complex.

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