Rifampicin antagonizes the effect of choloroquine on chloroquine-resistant Plasmodium berghei in mice.
Chloroquine (CQ)-resistant Plasmodium falciparum appears to decrease CQ accumulation in its food vacuole by enhancing its efflux via an active membrane pump, which has been reported to be a P-glycoprotein-like transporter. Rifampicin (RIF) is a P-glycoprotein inhibitor and also has some antimalarial activity. It is hoped that a combination of choloroquine-rifampicin (CQ + RIF) would be advantageous in the treatment of CQ-resistant malaria. Swiss albino mice were inoculated with CQ-resistant P. berghei intraperitoneally, and studied for the effect of CQ versus the combination of CQ + RIF at various doses on the clearance of parasitemia, the survival of the mice, and the recrudescence of malaria. Paradoxically, RIF decreased the survival rate and rate of clearance of parasitemia and increased the rate of recrudescence significantly when combined with various doses of CQ. Our results indicated that RIF worsened the course of the disease, and we concluded that RIF should not be combined with CQ in the treatment of malaria.
Hou
Low Jen
LJ
Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. jhlow@kck.usm.my
Raju
S Sivachandra
SS
Abdulah
M Shukri
MS
Nor
Norazmi M
NM
Ravichandran
M
M
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage*; D002738:Chloroquine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D010962:Plasmodium berghei / Q000187:drug effects*; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology*
D000962:Antimalarials; D002738:Chloroquine; D012293:Rifampin