Synergistic interaction between atovaquone and retinol in Plasmodium falciparum in vitro

Abstract

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, 65thand 80thpercentile 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 EC50values 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 EC90values 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. © 2007 Springer-Verlag.