Treatment of chloroquine-resistant malaria in monkeys with a drug combination that reverses resistance in vitro.
Compounds that inhibit the P-glycoprotein-related efflux mechanism of multidrug-resistant cells reverse chloroquine resistance in vitro. Hence, the co-administration of chloroquine and an efflux-blocking drug could potentially treat chloroquine-resistant malaria infections. We administered a drug combination (chloroquine and a tiapamil analogue), that has been shown to reverse chloroquine resistance in vitro, to Aotus monkeys but failed to safely clear experimentally-induced chloroquine-resistant Plasmodium falciparum parasitaemias.
Williams
H L
HL
Department of Hematology, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Johnson
D J
DJ
Okoye
V C
VC
Martin
S K
SK
D000818:Animals; D001029:Aotus trivirgatus; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002738:Chloroquine / Q000627:therapeutic use*; D004338:Drug Combinations; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011437:Propylamines / Q000627:therapeutic use*; D013997:Time Factors
D002121:Calcium Channel Blockers; D004338:Drug Combinations; D011437:Propylamines; C079672:Ro 11; D002738:Chloroquine