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CPT Pharmacometrics Syst Pharmacol. 2020 Mar 20. doi: 10.1002/psp4.12510. [Epub ahead of print]

Modeling favipiravir antiviral efficacy against emerging viruses: from animal studies to clinical trials.

Author information

1
Université de Paris, IAME, INSERM, F-75018, Paris, France.
2
UBIVE, Institut Pasteur, Centre International de Recherche en Infectiologie, Lyon, France.
3
Inserm, UMR 1219, Université de Bordeaux, Bordeaux, France.
4
Programme PACCI/site ANRS de Côte d'Ivoire, Abidjan, Côte d'Ivoire.
5
Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
6
German Center for Infection Research (DZIF), Partner Site Hamburg, Germany.
7
Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
8
UMR "Emergence des Pathologies Virales" (EPV, Aix-Marseille university - IRD 190 - Inserm 1207 - EHESP) - Institut Hospitalo-Universitaire Méditerranée Infection, F-13385, Marseille, France.
9
Center for Modeling and Simulation in the Biosciences (BIOMS), BioQuant-Center, Heidelberg University, Heidelberg, Germany.
10
Laboratoire P4 Inserm-Jean Mérieux, US003 Inserm, 69365, Lyon, France.

Abstract

In 2014, our research network was involved in the evaluation of favipiravir, an anti-Influenza polymerase inhibitor, against Ebola virus. In this review we discuss how mathematical modelling was used, first to propose a relevant dosing regimen in humans, and then to optimize its antiviral efficacy in a non-human primate (NHP) model. The data collected in NHPs were finally used to develop a model of Ebola pathogenesis integrating the interactions between the virus, the innate and adaptive immune response and the action of favipiravir. We conclude the review of this work by discussing how these results are of relevance for future human studies in the context of Ebola virus, but also for other emerging viral diseases for which no therapeutics are available.

PMID:
32198838
DOI:
10.1002/psp4.12510
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