Khandelwal, A. and Arez, F. and Alves, P. M. and Badolo, L. and Brito, C. and Fischli, C. and Fontinha, D. and Oeuvray, C. and Prudêncio, M. and Rottmann, M. and Wilkins, J. and Yalkinoglu, Ö. and Bagchus, W. M. and Spangenberg, T.. (2022) Translation of liver stage activity of M5717, a; Plasmodium; elongation factor 2 inhibitor: from bench to bedside. Malar J, 21. p. 151.
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Official URL: https://edoc.unibas.ch/90587/
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Abstract
BACKGROUND: Targeting the asymptomatic liver stage of Plasmodium infection through chemoprevention could become a key intervention to reduce malaria-associated incidence and mortality. METHODS: M5717, a Plasmodium elongation factor 2 inhibitor, was assessed in vitro and in vivo with readily accessible Plasmodium berghei parasites. In an animal refinement, reduction, replacement approach, the in vitro IC99 value was used to feed a Population Pharmacokinetics modelling and simulation approach to determine meaningful effective doses for a subsequent Plasmodium sporozoite-induced volunteer infection study. RESULTS: Doses of 100 and 200 mg would provide exposures exceeding IC99 in 96 and 100% of the simulated population, respectively. CONCLUSIONS: This approach has the potential to accelerate the search for new anti-malarials, to reduce the number of healthy volunteers needed in a clinical study and decrease and refine the animal use in the preclinical phase.
Faculties and Departments: | 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser) |
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UniBasel Contributors: | Fischli, Christoph and Rottmann, Matthias |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
ISSN: | 1475-2875 (Electronic)1475-2875 (Linking) |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
Related URLs: | |
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Last Modified: | 27 Dec 2022 10:44 |
Deposited On: | 27 Dec 2022 10:44 |
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