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Clinical Pharmacokinetics

, Volume 55, Issue 8, pp 907–923 | Cite as

Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials

  • Vincent Madelain
  • Thi Huyen Tram Nguyen
  • Anaelle Olivo
  • Xavier de Lamballerie
  • Jérémie Guedj
  • Anne-Marie Taburet
  • France MentréEmail author
Review Article

Abstract

The 2014–2015 outbreak of Ebola virus disease is the largest epidemic to date in terms of the number of cases, deaths, and affected areas. In October 2015, no antiviral agents had proven antiviral efficacy in patients. However, in September 2014, the World Health Organization inventoried and has since regularly updated a list of potential drug candidates with demonstrated antiviral efficacy in in vitro or animal models. This includes agents belonging to various therapeutic classes, namely direct antiviral agents (favipiravir and BCX4430), a combination of antibodies (ZMapp), type I interferons, RNA interference-based drugs (TKM-Ebola and AVI-7537), and anticoagulant drugs (rNAPc2). Here, we review the pharmacokinetic and pharmacodynamic information presently available for these drugs, using data obtained in healthy volunteers for pharmacokinetics and data obtained in human clinical trials or animal models for pharmacodynamics. Future studies evaluating these drugs in clinical trials are critical to confirm their efficacy in humans, propose appropriate doses, and evaluate the possibility of treatment combinations.

Keywords

Rhesus Macaque Cynomolgus Macaque Formal Safety Assessment EBOV Infection Peak Viral Load 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank Toyama Chemicals for providing us with the favipiravir pharmacokinetic data from their phase I clinical trials. We also wish to acknowledge Benoit Visseaux for his assistance with Fig. 2.

Compliance with Ethical Standards

Funding

This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 666092.

Conflicts of interest

The UMR 1137 research team, to which belong Vincent Madelain, Thi Huyen Tram Nguyen, Jeremie Guedj, and France Mentre, as well as Xavier de Lamballerie, received grants from the European Union and from Saint Luke University (Japan) to evaluate the PKPD of favipiravir in NHPs and in patients. THT Nguyen is conducting a post-doctoral research funded by the European Union project for favipiravir evaluation in Ebola virus patients. Anaelle Olivo and Anne-Marie Taburet declare that they have no conflict of interest related to the submitted manuscript.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Vincent Madelain
    • 1
    • 2
  • Thi Huyen Tram Nguyen
    • 1
    • 2
  • Anaelle Olivo
    • 3
  • Xavier de Lamballerie
    • 4
    • 5
  • Jérémie Guedj
    • 1
    • 2
  • Anne-Marie Taburet
    • 3
  • France Mentré
    • 1
    Email author
  1. 1.INSERM, IAME, UMR 1137ParisFrance
  2. 2.Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris CitéParisFrance
  3. 3.Hospital Bicêtre, Assistance Publique-Hôpitaux de Paris, DHU Hepatinov, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-SudKremlin BicêtreFrance
  4. 4.Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 “Emergence des Pathologies Virales”MarseilleFrance
  5. 5.Institut Hospitalo-Universitaire Méditerranée InfectionMarseilleFrance

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