title: In vitro interaction of lumefantrine and piperaquine by atorvastatin against Plasmodium falciparum.
abstract: BACKGROUND
  There is an urgent need for the discovery of new anti-malarial drugs and combination therapy. A combinatorial approach protects each drug from the development of resistance and reduces generally the overall transmission rate of malaria. Statins, the inhibitors of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase and a family of lipid-lowering drugs, have in vitro anti-malarial properties, and more specially atorvastatin. However, atorvastatin has a short elimination half-life (14 hours) and an efficient combination of anti-malarial drugs must associate a drug with a short elimination half-life and a drug with a long elimination half-life. The objective of the present work was to identify new potential partners among standard new anti-malarial drugs with long elimination half-life, such as lumefantrine, piperaquine, pyronaridine and atovaquone, to improve the in vitro activity of atorvastatin against different Plasmodium falciparum strains to treat uncomplicated malaria.
  
  
  METHODS
  In vitro interaction of atorvastatin in combination with lumefantrine, piperaquine, pyronaridine and atovaquone was assessed against 13 P. falciparum strains by isotopic test.
  
  
  RESULTS
  Atorvastatin showed additive effects with pyronaridine, piperaquine and lumefantrine. Atorvastatin increased the in vitro activity of lumefantrine and piperaquine at concentrations expected in clinical observations. The average IC50 values of lumefantrine decreased significantly from 31.9 nM to 20.5 nM (a decrease of 35.7%) in combination with 1 μM of atorvastatin.
  
  
  CONCLUSIONS
  Even though in vitro data indicate that atorvastatin improved the activity of lumefantrine and piperaquine, the same may not necessarily be true in vivo. Piperaquine, a new drug with long terminal elimination half-life, is currently a very promising anti-malarial drug.
authors.forename: Jérome
authors.initials: J
authors.lastname: Dormoi
authors.forename: Hélène
authors.initials: H
authors.lastname: Savini
authors.forename: Rémy
authors.initials: R
authors.lastname: Amalvict
authors.forename: Eric
authors.initials: E
authors.lastname: Baret
authors.affiliation: Unité de Parasitologie et d'Entomologie, Département de Microbiologie, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France. bruno.pradines@free.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D000069059:Atorvastatin; D004357:Drug Synergism; D004983:Ethanolamines / Q000494:pharmacology*; D005449:Fluorenes / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D000078102:Lumefantrine; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D010879:Piperazines
chemical_list: D000962:Antimalarials; D000069059:Atorvastatin; D004983:Ethanolamines; D005449:Fluorenes; D006538:Heptanoic Acids; D000078102:Lumefantrine; D011758:Pyrroles; D011804:Quinolines; C034759:piperaquine; D010879:Piperazines