Pharmacodynamic interaction between mefloquine and retinol in Plasmodium falciparum in vitro

Abstract

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, 65thand 80thpercentile of the physiological retinol levels in healthy adults was determined in 37 fresh isolates of P. falciparum. The mean IC50, IC90and IC99values 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. © 2009 Springer-Verlag.