title: Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials.
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.
authors.affiliation: INSERM, IAME, UMR 1137, Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Madelain
authors.affiliation: INSERM, IAME, UMR 1137, Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France.
authors.forename: Thi Huyen Tram
authors.initials: TH
authors.lastname: Nguyen
authors.affiliation: Hospital Bicêtre, Assistance Publique-Hôpitaux de Paris, DHU Hepatinov, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud, Kremlin Bicêtre, France.
authors.forename: Anaelle
authors.initials: A
authors.lastname: Olivo
authors.affiliation: Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 "Emergence des Pathologies Virales", Marseille, France.|Institut Hospitalo-Universitaire Méditerranée Infection, Marseille, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: de Lamballerie
authors.affiliation: INSERM, IAME, UMR 1137, Paris, France.|Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Guedj
authors.affiliation: Hospital Bicêtre, Assistance Publique-Hôpitaux de Paris, DHU Hepatinov, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Sud, Kremlin Bicêtre, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
authors.affiliation: INSERM, IAME, UMR 1137, Paris, France. france.mentre@inserm.fr.
authors.forename: France
authors.initials: F
authors.lastname: Mentré
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000241:Adenosine / Q000031:analogs & derivatives; D000577:Amides / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D004196:Disease Outbreaks / Q000517:prevention & control; D029043:Ebolavirus / Q000187:drug effects; D064368:Healthy Volunteers; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D023421:Models, Animal; D011684:Purine Nucleosides / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D011719:Pyrazines / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D011759:Pyrrolidines
chemical_list: D000577:Amides; D000998:Antiviral Agents; D011684:Purine Nucleosides; D011719:Pyrazines; D011759:Pyrrolidines; C462182:favipiravir; D000225:Adenine; D000241:Adenosine; C517546:galidesivir