Publication: The effects of serum lipids on the in vitro activity of lumefantrine and atovaquone against Plasmodium falciparum
1
Accepted Date
2012-04-25
Issued Date
2012-05-28
Copyright Date
2012
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
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Mahidol University
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BioMed Central
Bibliographic 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.
Suggested Citation
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. The effects of serum lipids on the in vitro activity of lumefantrine and atovaquone against Plasmodium falciparum. 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.. doi:10.1186/1475-2875-11-177 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/709
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Title
The effects of serum lipids on the in vitro activity of lumefantrine and atovaquone against Plasmodium falciparum
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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.