HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Impact of cerebral malaria on brain distribution of mefloquine.

Abstract
Cerebral malaria (CM) is the most severe complication of Plasmodium falciparum malaria. The aim of this study was to investigate the influence of CM on the cerebral uptake of mefloquine (MQ), in an experimental model of mice infected with Plasmodium berghei ANKA (PbA). Drug diffusion in brain is closely related to efflux pumps such as P-glycoprotein (P-gp/ABCB1/MDR1) and Breast Cancer Resistant Protein (BCRP/ABCG2), two major components of the blood-brain barrier (BBB) which can be modified by inflammation and/or infection. After a single IP dose, MQ concentrations were measured by liquid chromatography in blood and brains of mice infected with Plasmodium berghei ANKA and compared with that of non-infected mice. Our results show that MQ brain concentrations were decreased in CM mice versus healthy mice (0.77 versus 1.31 for brain/plasma concentrations). Although MQ is transported out of endothelial cells by P-glycoprotein, this result cannot be related to this transporter as we have previously shown that CM does not alter P-gp function (personal data). CM induces a reduction of MQ brain transport and, therefore, an increase of central toxicity due to MQ should not be expected during CM.
AuthorsSylvie Barraud de Lagerie, Christine Fernandez, Michèle German-Fattal, Jean-Charles Gantier, François Gimenez, Robert Farinotti
JournalDrug metabolism letters (Drug Metab Lett) Vol. 3 Issue 1 Pg. 15-7 (Jan 2009) ISSN: 1874-0758 [Electronic] United Arab Emirates
PMID19356112 (Publication Type: Journal Article)
Chemical References
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antimalarials
  • Mefloquine
Topics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
  • Animals
  • Antimalarials (pharmacokinetics)
  • Blood-Brain Barrier
  • Brain (metabolism)
  • Chromatography, High Pressure Liquid
  • Erythrocytes (parasitology)
  • Female
  • Malaria, Cerebral (metabolism, parasitology)
  • Mefloquine (pharmacokinetics)
  • Mice
  • Mice, Inbred C57BL
  • Plasmodium berghei (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: