Pharmacodynamic interaction between 4-aminoquinolines and retinol in Plasmodium falciparum in vitro.
The pharmacodynamic interaction between retinol and 4-aminoquinolines has been investigated in 29 fresh isolates of Plasmodium falciparum. Although the parasites were highly resistant against 4-aminoquinolines, significant synergism was observed between chloroquine and retinol as well as amodiaquine and retinol, the latter at physiological concentrations. Combination with retinol reduced the geometric mean concentrations effecting complete inhibition (GMCOC) by chloroquine from 14425 nM to 8943 nM in CHL-RET low, 7042 nM in CHL-RET medium, and 4920 nM in CHL-RET high. Synergism between amodiaquine and retinol was greater, with strong and highly significant reductions of the GMCOC, from 2520 nM for amodiaquine to 1092 nM for AMO-RET low, 800 nM for AMO-RET medium, and 745 nM for AMO-RET high. While it is obviously too late for making practical use of the activity enhancement for chloroquine, the situation is different for amodiaquine, where supplementation with retinol may extend the usefulness of the medicament.
Ley
Benedikt
B
Department of Anthropology, Faculty of Life Sciences, University of Vienna, Austria.
Wernsdorfer
Gunther
G
Frank
Christine
C
Sirichaisinthop
Jeeraphat
J
Congpuong
Kanungnit
K
Wernsdorfer
Walther H
WH
D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000655:Amodiaquine / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D002738:Chloroquine / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D066298:In Vitro Techniques; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013785:Thailand; D014801:Vitamin A / Q000737:chemistry / Q000494:pharmacology*; D014815:Vitamins / Q000737:chemistry / Q000494:pharmacology*
D000634:Aminoquinolines; D000962:Antimalarials; D014815:Vitamins; D014801:Vitamin A; D000655:Amodiaquine; D002738:Chloroquine; C001920:4-aminoquinoline