Jpn. J. Infect. Dis., 57, 198-202, 2004
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Original Article
Rifampicin Antagonizes the Effect of Chloroquine on Chloroquine-Resistant Plasmodium berghei in Mice
Low Jen Hou*, S. Sivachandra Raju, M. Shukri Abdullah1, Norazmi M. Nor2 and M. Ravichandran1
Department of Pharmacology and 1Department of Microbiology, School of Medical Sciences and 2School of Health Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
(Received February 16, 2004. Accepted June 3, 2004)
*Corresponding author: Mailing address: Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. Tel: +60-9-7664703, Fax: +60-9-7653370, E-mail: jhlow@kck.usm.my
SUMMARY: 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.