Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials
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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.
KeywordsRhesus Macaque Cynomolgus Macaque Formal Safety Assessment EBOV Infection Peak Viral Load
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
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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