Pharmacodynamic interaction between mefloquine and retinol in Plasmodium falciparum in vitro.

Wien Klin Wochenschr 2009 Oct;121 Suppl 3:27-31

Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.

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 50(th), 65(th) and 80(th) percentile of the physiological retinol levels in healthy adults was determined in 37 fresh isolates of P. falciparum. The mean IC(50), IC(90) and IC(99) values for mefloquine were 1.76, 9.81 and 39.78 microM, those for mefloquine + retinol "low" 0.33, 1.37 and 4.33 microM, those for mefloquine + retinol "medium" 0.29, 1.15 and 3.48 microM, and those for mefloquine + retinol "high" 0.20, 0.85 and 2.70 microM. Evidence for strong synergism between mefloquine and retinol in P. falciparum was highly significant.

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http://dx.doi.org/10.1007/s00508-009-1231-6DOI Listing
October 2009
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References

(Supplied by CrossRef)

EF Boudreau et al.
Lancet 1982

WH Wernsdorfer et al.
Pharmac Ther 1991

RN Price et al.
Trans R Soc Trop Med Hyg 1997

H Noedl et al.
N Engl J Med 2008

P Lim et al.
Malar J 2009

WO Rogers et al.
Malar J 2009

A Metzger et al.
Am J Trop Med Hyg 2001

DI Thurnham et al.
Trans R Soc Trop Med Hyg 1991

TM Davis et al.
Clin Sci (Lond) 1004

BS Das et al.
Am J Clin Nutr 1996

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