The effects of serum lipids on the in vitro activity of lumefantrine and atovaquone against Plasmodium falciparum

Malaria Journal

Research

Mathirut Mungthin¹  Rachanee Udomsangpetch²  Pratap Singhasivanon³  Kesinee Chotivanich³  Arjen M Dondorp³  Sasithon Pukrittayakamee³  Nicholas J White⁴  Ronnatrai Ruengweerayuth⁵ 

[1] Department of Parasitology, Phramongkutklao College of Medicine, 315 Rajvithi Rd, 10400, Bangkok, Thailand;Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand;MORU, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, 10400, Bangkok, Thailand;MORU, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd, 10400, Bangkok, Thailand;Centre for Tropical Medicine, Churchill Hospital. University of Oxford, Oxford, UK;Mae Sot Hospital, Tak, Thailand;

关键词: Malaria;    Anti-malarial drugs;    In vitro;   

DOI  :  10.1186/1475-2875-11-177

 received in 2011-12-30, accepted in 2012-04-25,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundLumefantrine 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.MethodsSerum 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 3H-hypoxanthine uptake inhibition method and expressed as the concentration which gave 50% inhibition of hypoxanthine uptake (IC50).ResultsDoubling plasma triglyceride concentrations (from 160 mg/dL to 320 mg/dL), resulted in an approximate doubling of the IC50 for lumefantrine (191 ng/mL to 465 ng/mL, P < 0.01) and a 20-fold increase in the IC50 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 the medium.ConclusionsLipidaemia 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.

【 授权许可】

Unknown   
© Chotivanich et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.