Spezifische pharmakodynamische Interaktion zwischen Atovaquon und Retinol bei Plasmodium falciparum

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, 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 EC(50) 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 EC(90) 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 282.5 nM, 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.

Synergism between pyronaridine and retinol in Plasmodium falciparum in vitro

“…Since retinol exerts blood schizontocidal activity in Plasmodium falciparum [6] and potentiates the eff ect of antimalarial drugs such as artemisinin, atovaquone and quinine [7][8][9], it was therefore plausible to investigate the interaction between retinol and pyronaridine.…”

Synergism between quinine and retinol in fresh isolates of Plasmodium falciparum

“…As earlier studies have yielded evidence of activity of retinol against P. falciparum in vitro [7] as well as synergistic interaction be tween retinol (Fig. 2) and various blood schizontocidal compounds such as monodesbutylbenflumetol, atova quone as well as artemisinin [8][9][10][11], it was of interest to investigate whether this phenomenon extends also to 4quinolinemethanols such as quinine -the secondary objective of the study.…”

Pharmacodynamic interaction between 4-aminoquinolines and retinol in Plasmodium falciparum in vitro

“…Recently, significant synergism has been observed between retinol (Fig. 2) and atovaquone [5], artemisinin [6], and monodesbutyl-benflumetol [7,8] in P. falciparum. It was therefore of interest wkw Pharmacodynamic interaction between 4-aminoquinolines and retinol 19-20/2008 original article 75 to find out whether retinol increases also the blood schizontocidal activity of 4-aminoquinolines in natural P. falciparum isolates showing marked resistance to chloroquine and amodiaquine.…”