title: 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 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.
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Gruber
authors.forename: Gunther
authors.initials: G
authors.lastname: Wernsdorfer
authors.forename: Wichai
authors.initials: W
authors.lastname: Satimai
authors.forename: Ursula
authors.initials: U
authors.lastname: Wiedermann
authors.forename: Kanungnit
authors.initials: K
authors.lastname: Congpuong
authors.forename: Walther H
authors.initials: WH
authors.lastname: Wernsdorfer
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007928:Lethal Dose 50; D015767:Mefloquine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism*; D014801:Vitamin A / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000962:Antimalarials; D014801:Vitamin A; D015767:Mefloquine