Dose-dependent effect and pharmacokinetics of fexinidazole and its metabolites in a mouse model of human african trypanosomiasis.


Burrell-Saward, H; Harris, AJ; de LaFlor, R; Sallam, H; Alavijeh, MS; Ward, TH; Croft, SL; (2017) Dose-dependent effect and pharmacokinetics of fexinidazole and its metabolites in a mouse model of human african trypanosomiasis. International journal of antimicrobial agents. ISSN 0924-8579 DOI: 10.1016/j.ijantimicag.2017.01.038

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Abstract

Human African trypanosomiasis (HAT) is a neglected tropical disease, with a population of 70 million at risk. Current treatment options are limited. In the search for new therapeutics, the repurposing of the broad-spectrum antiprotozoal drug fexinidazole has completed Phase III trials with the anticipation that it will be the first oral treatment for HAT. This study used the recently validated bioluminescence imaging model to assess the dose and rate of kill effect of fexinidazole in infected mice, and the dose-dependent effect of fexinidazole on trypanosome infection. Pharmacokinetics of fexinidazole in plasma and central nervous system (CNS) compartments were similar in both infected and uninfected mice. Drug distribution within the CNS was further examined by microdialysis, showing similar levels in the cortex and hippocampus. However, high variability in drug distribution and exposure was found between mice.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Antimicrobial Resistance Centre (AMR)
Leishmaniasis Group
Neglected Tropical Diseases Network
PubMed ID: 28552771
URI: http://researchonline.lshtm.ac.uk/id/eprint/3928343

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