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Trends Pharmacol Sci. 2006 Nov;27(11):594-601. Epub 2006 Sep 25.

Transporters involved in resistance to antimalarial drugs.

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1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Abstract

The ability to treat and control Plasmodium falciparum infection through chemotherapy has been compromised by the advent and spread of resistance to antimalarial drugs. Research in this area has identified the P. falciparum chloroquine resistance transporter (PfCRT) and the multidrug resistance-1 (PfMDR1) transporter as key determinants of decreased in vitro susceptibility to several principal antimalarial drugs. Transfection-based in vitro studies are consistent with clinical findings of an association between mutations in the pfcrt gene and failure of chloroquine treatment, and between amplification of the pfmdr1 gene and failure of mefloquine treatment. Many countries are now switching to artemisinin-based combination therapies. These incorporate partner drugs of which some have an in vitro efficacy that can be modulated by changes in pfcrt or pfmdr1. Here, we summarize investigations of these and other recently identified P. falciparum transporters in the context of antimalarial mode of action and mechanisms of resistance.

PMID:
16996622
PMCID:
PMC2944664
DOI:
10.1016/j.tips.2006.09.005
[Indexed for MEDLINE]
Free PMC Article
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