Kesinee ChotivanichMathirut MungthinRonnatrai RuengweerayuthRachanee UdomsangpetchArjen M. DondorpPratap SinghasivanonSasithon PukrittayakameeNicholas J. WhiteMahidol UniversityPhramongkutklao College of MedicineMae Sot General HospitalUniversity of Oxford2018-06-112018-06-112012-05-29Malaria Journal. Vol.11, (2012)147528752-s2.0-84861439370https://repository.li.mahidol.ac.th/handle/123456789/14317Background: 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.Mahidol UniversityImmunology and MicrobiologyMedicineArticleSCOPUS10.1186/1475-2875-11-177