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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/14317
Title: The effects of serum lipids on the in vitro activity of lumefantrine and atovaquone against Plasmodium falciparum
Authors: Kesinee Chotivanich
Mathirut Mungthin
Ronnatrai Ruengweerayuth
Rachanee Udomsangpetch
Arjen M. Dondorp
Pratap Singhasivanon
Sasithon Pukrittayakamee
Nicholas J. White
Mahidol University
Phramongkutklao College of Medicine
Mae Sot General Hospital
University of Oxford
Keywords: Immunology and Microbiology;Medicine
Issue Date: 29-May-2012
Citation: Malaria Journal. Vol.11, (2012)
Abstract: Background: Lumefantrine and atovaquone are highly lipophilic anti-malarial drugs. As a consequence absorption is increased when the drugs are taken together with a fatty meal, but the free fraction of active drug decreases in the presence of triglyceride-rich plasma lipoproteins. In this study, the consequences of lipidaemia on anti-malarial drug efficacy were assessed in vitro. Methods: Serum was obtained from non-immune volunteers under fasting conditions and after ingestion of a high fat meal and used in standard Plasmodium falciparum in-vitro susceptibility assays. Anti-malarial drugs, including lumefantrine, atovaquone and chloroquine in five-fold dilutions (range 0.05 ng/ml 1 ug/mL) were diluted in culture medium supplemented with fasting or post-prandial 10% donor serum. The in-vitro drug susceptibility of parasite isolates was determined using the 3 H-hypoxanthine uptake inhibition method and expressed as the concentration which gave 50% inhibition of hypoxanthine uptake (IC 50 ). Results: Doubling plasma triglyceride concentrations (from 160 mg/dL to 320 mg/dL), resulted in an approximate doubling of the IC 50 for lumefantrine (191 ng/mL to 465 ng/mL, P < 0.01) and a 20-fold increase in the IC 50 for atovaquone (0.5 ng/mL to 12 ng/ml; P < 0.01). In contrast, susceptibility to the hydrophilic anti-malarial chloroquine did not change in relation to triglyceride content of th e medium. Conclusions: Lipidaemia reduces the anti-malarial activity of lipophilic anti-malarial drugs. This is an important confounder in laboratory in vitro testing and it could have therapeutic relevance. Keywords: Malaria, Anti-malarial drugs, In vitro-susceptibility © 2012 Chotivanich et al.; licensee BioMed Central Ltd.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84861439370&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/14317
ISSN: 14752875
Appears in Collections:Scopus 2011-2015

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