Simple jQuery Dropdowns
Please use this identifier to cite or link to this item:
Title: The effects of serum lipids on the in vitro activity of lumefantrine and atovaquone against Plasmodium falciparum
Authors: Kesinee Chotivanich
เกศินี โชติวานิช
Mathirut Mungthin
มฑิรุทธ มุ่งถิ่น
Ronnatrai Ruengweerayuth
Rachanee Udomsangpetc
รัชนีย์ อุดมแสงเพ็ชร
Dondorp, Arjen M.
Pratap Singhasivanon
ประตาป สิงหศิวานนท์
Sasithon Pukrittayakamee
ศศิธร ผู้กฤตยาคามี
White, Nicholas J.
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit
Mahidol University. Faculty of Science. Department of Pathobiology
White, Nicholas J.
Keywords: Anti-malarial drugs;In vitro-susceptibility;Malaria;Open Access article
Issue Date: 28-May-2012
Citation: Chotivanich K, Mungthin M, Ruengweerayuth R, Udomsangpetch R, Dondorp AM, Singhasivanon P, et al. The effects of serum lipids on the in vitro activity of lumefantrine and atovaquone against Plasmodium falciparum. Malar J. 2012 May 28;11:177.
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 ³H-hypoxanthine uptake inhibition method and expressed as the concentration which gave 50% inhibition of hypoxanthine uptake (IC₅₀). RESULTS: Doubling 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. 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.
ISSN: 1475-2875 (electronic)
Appears in Collections:TM-Article

Files in This Item:
File Description SizeFormat 
tm-ar-kesinee-2012.pdf224.2 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.