An Analytical Evaluation Of In Vitro Drug-Drug Interaction Studies For Fixed Artesunate Combination Therapy
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Date
2010-04
Authors
Daniel Jayaraj, Vanessa Shalini
Journal Title
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Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Drug-resistant Plasmodium falciparum has become a serious threat, especially in malaria-endemic regions of the world. In light of this, the WHO has recommended artemisinin combination therapy such as artesunate-mefloquine and artesunate-amodiaquine as first line treatment for uncomplicated falciparum malaria especially in regions harbouring the most resistant isolates. However, the in vitro drug interaction studies have not been conducted for both these combinations.
An in vitro experimental technique, utilizing human liver microsomes was used to study the metabolism of AS in the presence and absence of mefloquine and amodiaquine. Simultaneous determination of artesunate, dihydroartemisinin and artemisinin in microsomal sample was performed using high performance liquid chromatography- electrochemical (HPLC-EC) method. The study shows that artesunate is metabolised to dihydroartemisinin in the in vitro microsomal assay. The reaction is mediated by CYP450 enzymes present in the microsomal assay.
The metabolism of artesunate was not affected by mefloquine or amodiaquine at therapeutic concentrations using the in vitro microsomal technique. The absence of interactions between these drugs led to the conclusion that the artesunate-mefloquine and artesunate-amodiaquine combinations are ideal and safe treatments when used in therapeutic concentrations. However, further clinical studies must be done to confirm these findings.
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Keywords
An analytical evaluation of in vitro drug-drug interaction , for fixed artesunate combination therapy